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Li K, Chen J, Li W, Zhang Z, Xue Y, Zheng Y, Zhang Y, Zhang C, Bergan R, Zhao L. KBU2046 exerts inhibition on chemokine gradient-mediated motility of esophageal squamous cell carcinoma through reducing integrin expression. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167800. [PMID: 40118292 DOI: 10.1016/j.bbadis.2025.167800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 03/08/2025] [Accepted: 03/11/2025] [Indexed: 03/23/2025]
Abstract
Esophageal squamous cell carcinoma (ESCC) cells migrate from their initial site of origin, ultimately forming metastasis and causing death. The selective inhibition of ESCC cell movement has not been possible to date. Here we demonstrate that the small molecule therapeutic agent KBU2046 inhibits the characteristic migration and invasion of ESCC cells induced by chemokine gradients, having no effect on cell proliferation. After demonstrating that KBU2046 inhibits human ESCC metastasis in a murine model, we showed that it doesn't inhibit the in vitro efficacy of chemotherapeutic agents used clinically, going on to demonstrate maintenance of cisplatin efficacy when combined with KBU2046 in a murine model. Mechanistic studies demonstrated that KBU2046 inhibited epidermal growth factor (EGF)-mediated phosphorylation of receptor-interacting serine/threonine protein kinase 1 (RIPK1) on its Ser166 activation motif. RIPK1 was shown to be necessary for KBU2046 efficacy. However, this was shown to be dependent upon cell context, and was also shown to be dependent upon level of RIPK1 expression, both supporting the presence of additional therapeutically sensitive regulatory pathways. Mass spectrometry analysis of ESCC cells demonstrated that KBU2046 selectively altered the expression of proteins involved in cell motility. Integrin αV (ITGAV) is overexpressed in ESCC, was decreased by KBU2046, and its knockdown inhibited ESCC cell migration and invasion, which was necessary for KBU2046 efficacy. We demonstrate that ESCC's motility can be inhibited, and KBU2046 inhibits motility in an Integrin αV-dependent manner, and that combining anti-motility and cytotoxic agents is a high valuable therapeutic strategy for ESCC that should be further developed.
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Affiliation(s)
- Kexin Li
- Research center, The Key Laboratory of Tumor Gene Diagnosis and Treatment, the Fourth Hospital of Hebei University, Shijiazhuang 050011, China
| | - Jinxia Chen
- Research center, The Key Laboratory of Tumor Gene Diagnosis and Treatment, the Fourth Hospital of Hebei University, Shijiazhuang 050011, China
| | - Wendi Li
- Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon 97239, United States
| | - Zhenzhen Zhang
- Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon 97239, United States
| | - Yongxian Xue
- Research center, The Key Laboratory of Tumor Gene Diagnosis and Treatment, the Fourth Hospital of Hebei University, Shijiazhuang 050011, China
| | - Yang Zheng
- Research center, The Key Laboratory of Tumor Gene Diagnosis and Treatment, the Fourth Hospital of Hebei University, Shijiazhuang 050011, China
| | - Ying Zhang
- Department of Pathology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
| | - Cong Zhang
- Research center, The Key Laboratory of Tumor Gene Diagnosis and Treatment, the Fourth Hospital of Hebei University, Shijiazhuang 050011, China
| | - Raymond Bergan
- Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon 97239, United States.
| | - Lianmei Zhao
- Research center, The Key Laboratory of Tumor Gene Diagnosis and Treatment, the Fourth Hospital of Hebei University, Shijiazhuang 050011, China; Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon 97239, United States.
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2
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Wang H, Ardila C, Jindal A, Aggarwal V, Wang W, Vande Geest J, Jiang Y, Xing J, Sant S. Protrusion force and cell-cell adhesion-induced polarity alignment govern collective migration modes. Biophys J 2025; 124:1674-1692. [PMID: 40235119 DOI: 10.1016/j.bpj.2025.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 02/28/2025] [Accepted: 04/10/2025] [Indexed: 04/17/2025] Open
Abstract
Collective migration refers to the coordinated movement of cells as a single unit during migration. Although collective migration enhances invasive and metastatic potential in cancer, the mechanisms driving this behavior and regulating tumor migration plasticity remain poorly understood. This study provides a mechanistic model explaining the emergence of different modes of collective migration under hypoxia-induced secretome. We focus on the interplay between cellular protrusion force and cell-cell adhesion using collectively migrating three-dimensional microtumors as models with well-defined microenvironments. Large microtumors show directional migration due to intrinsic hypoxia, whereas small microtumors exhibit radial migration when exposed to hypoxic secretome. Here, we developed an in silico multi-scale microtumor model based on the cellular Potts model and implemented in CompuCell3D to elucidate underlying mechanisms. We identified distinct migration modes within specific regions of protrusion force and cell-cell adhesion parameter space and studied these modes using in vitro experimental microtumor models. We show that sufficient cellular protrusion force is crucial for radial and directional collective microtumor migration. Radial migration emerges when sufficient cellular protrusion force is generated, driving neighboring cells to move collectively in diverse directions. Within migrating tumors, strong cell-cell adhesion enhances the alignment of cell polarity, breaking the symmetric angular distribution of protrusion forces and leading to directional microtumor migration. The integrated results from the experimental and computational models provide fundamental insights into collective migration in response to different microenvironmental stimuli. Our computational and experimental models can adapt to various scenarios, providing valuable insights into cancer migration mechanisms.
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Affiliation(s)
- Huijing Wang
- Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Catalina Ardila
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Ajita Jindal
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Vaishali Aggarwal
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Weikang Wang
- Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing, China; School of Physical Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Jonathan Vande Geest
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Yi Jiang
- Department of Mathematics and Statistics, Georgia State University, Atlanta, Georgia
| | - Jianhua Xing
- Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, Pennsylvania; UPMC-Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
| | - Shilpa Sant
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; UPMC-Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmaceutical Sciences, Retzky College of Pharmacy, University of Illinois Chicago, Chicago, Illinois.
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3
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Li Y, Zhang R, Dang Y, Liang Y, Wang L, Chen N, Zhuang L, Liu W, Gong T. Sieging tumor cells using an amorphous ferric coordination polymer. MATERIALS HORIZONS 2025; 12:3388-3398. [PMID: 40025991 DOI: 10.1039/d4mh01558d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/04/2025]
Abstract
Metastasis is one of the main reasons for cancer treatment failure. Unfortunately, most treatment approaches inevitably damage the extracellular matrix (ECM) during tumor cell elimination, thereby augmenting the risk of metastasis. Herein, we proposed a "sieging tumor cells" strategy based on ferric coordination polymers (FeCPs), which involved anchoring tumor cells through ECM consolidation and selectively eliminating them in the tumor regions. Due to the weak coordination interactions and amorphous structure of FeCPs, the acidic tumor microenvironment facilitated their disintegration, releasing salicylic acid (SA), 2,5-dihydroxyterephthalic acid (DHTA) and Fe3+ ions. The released SA inhibited heparinase activity to consolidate the ECM, while Fe-mediated chemodynamic therapy (CDT) was enhanced by DHTA due to its fast electron transport behavior, ultimately inhibiting tumor growth and metastasis. The results from the orthotopic 4T1 breast tumor model indicated that lung metastasis was reduced by about 90%, and the survival rate improved by 70% after FeCP treatment. Overall, this "sieging tumor cells" strategy provides an emerging approach for the treatment of malignant tumors by consolidating the ECM in combination with self-enhanced CDT.
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Affiliation(s)
- Yanli Li
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
| | - Ruoqi Zhang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
| | - Yuanye Dang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
| | - Yongyu Liang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
| | - Lulu Wang
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
| | - Na Chen
- Soochow University Library, Soochow University, Suzhou 215006, China
| | - Luwen Zhuang
- Center for Water Resources and Environment, and Guangdong Key Laboratory of Marine Civil Engineering, School of Civil Engineering, Sun Yat-sen University, Guangzhou 510275, China.
| | - Wen Liu
- School of Public Health, Guangzhou Medical University, Guangzhou 511436, China.
| | - Teng Gong
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
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4
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Ji X, Qian X, Luo G, Yang W, Huang W, Lei Z, Zhou J, Zhong G, Zhou J, Liu N, Ma L, Li M, Liu X, Wu S, Zhang Y. Engineered macrophage nanoparticles enhance microwave ablation efficacy in osteosarcoma via targeting the CD47-SIRPα Axis: A novel Biomimetic immunotherapeutic approach. Bioact Mater 2025; 47:248-265. [PMID: 39925711 PMCID: PMC11803168 DOI: 10.1016/j.bioactmat.2025.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 12/30/2024] [Accepted: 01/12/2025] [Indexed: 02/11/2025] Open
Abstract
Osteosarcoma (OS) is a lethal bone tumor that primarily affects adolescents. OS is characterized by a high incidence of recurrence following surgical intervention, which is attributed to the presence of residual microscopic disease. Tumor-associated macrophages, which dominate the tumor microenvironment, often suppress immune responses and facilitate tumor progression and recurrence. This study developed an innovative nanotherapeutic approach by utilizing genetically engineered macrophage membranes with M1 polarization, stably overexpressing signal regulatory protein alpha (SIRPα), to encapsulate microwave-responsive nano-Prussian blue (SIRPα-M@nanoPB) nanoparticles. These nanoparticles induce tumor cell death selectively through hyperthermia and microwave dynamic effects upon targeted microwave irradiation. It is of critical importance to note that the enhancement of SIRPα on the nanoparticle surface actively targets and binds CD47 of tumor cells, thereby disrupting the "don't-eat-me" signal and effectively countering the immunosuppressive tumor environment. This action restores macrophage phagocytosis with M1 polarization, triggering potent immune responses. Our strategy holds considerable promise when it comes to improving the efficacy of microwave ablation through immune modulation, while reducing thermal damage to adjacent normal tissue and minimizing the risk of tumor recurrence. Thus, it offers a significant advancement in microwave therapies for patients with OS.
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Affiliation(s)
- Xiongfa Ji
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Xin Qian
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No.168 Litang Road, Changping District, 100000, Beijing, China
| | - Guowen Luo
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Wenjie Yang
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Wenhan Huang
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Zehua Lei
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Jiaqi Zhou
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Guoqing Zhong
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Jielong Zhou
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Nan Liu
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Limin Ma
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Mei Li
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
| | - Xiangmei Liu
- School of Health Science & Biomedical Engineering, Hebei University of Technology, Xiping Avenue 5340, 300401, Tianjin, China
| | - Shuilin Wu
- School of Materials Science & Engineering, Peking University, Yi-He-Yuan Road 5, 100871, Beijing, China
| | - Yu Zhang
- Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
- Guang Dong Engineering Technology Research Center of Functional, Repair of Bone Defects and Biomaterials, 510080, Guangzhou, China
- Medical Research Center, Department of Orthopedics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, 510080, Guangzhou, China
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5
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Tan W, Zhu Y, Chen S. Innovative approach to the detection of circulating tumor biomarkers: multi-dimensional application of liposome technology. Lipids Health Dis 2025; 24:160. [PMID: 40295973 PMCID: PMC12036244 DOI: 10.1186/s12944-025-02578-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 04/19/2025] [Indexed: 04/30/2025] Open
Abstract
Malignant tumors represent a significant worldwide health challenge, with elevated morbidity and mortality rates necessitating enhanced early identification and individualized treatment. Liposomes, as biomimetic lipid-based nanovesicles, have developed as a multifaceted platform for detecting and treating malignant tumors due to their excellent biocompatibility, stability, and membrane fusion properties. Circulating tumor markers, such as circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor proteins (CTPs), and circulating tumor nucleic acids (ctNAs), play a key role in early cancer diagnosis, disease progression monitoring, and personalized therapy. Liposome-based platforms enable effective molecular recognition, targeted detection, and signal amplification by targeting circulating tumor biomarkers, significantly increasing the potential for early tumor diagnosis and treatment. This review systematically summarizes advancements in the study of liposomes concerning circulating tumor markers, including applications in targeted recognition, early detection, and disease diagnosis, while discussing present problems and prospective applications of existing technology.
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Affiliation(s)
- Weichu Tan
- Department of Laboratory Medicine, Medical Research Center of Nanfang Hospital, School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Provincial Key Laboratory of Single-Cell and Extracellular Vesicles, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China
| | - Yitong Zhu
- Department of Laboratory Medicine, Medical Research Center of Nanfang Hospital, School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Provincial Key Laboratory of Single-Cell and Extracellular Vesicles, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China
| | - Siting Chen
- Department of Laboratory Medicine, Medical Research Center of Nanfang Hospital, School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Provincial Key Laboratory of Single-Cell and Extracellular Vesicles, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.
- The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People's Republic of China.
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6
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Farhadi P, Park T. The p130Cas-Crk/CrkL Axis: A Therapeutic Target for Invasive Cancers Unveiled by Collaboration Among p130Cas, Crk, and CrkL. Int J Mol Sci 2025; 26:4017. [PMID: 40362257 PMCID: PMC12071665 DOI: 10.3390/ijms26094017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Revised: 04/15/2025] [Accepted: 04/16/2025] [Indexed: 05/15/2025] Open
Abstract
Numerous studies have documented the involvement of p130Cas (Crk-associated substrate) in a wide range of cellular processes across different types of cells. These processes encompass cell transformation, the connection between the extracellular matrix and the actin cytoskeleton, cell migration and invasion, and cardiovascular development. Moreover, p130Cas has been associated with the regulation of various physiological processes, including mammary, bone, brain, muscle, and liver homeostasis. The diverse functions of p130Cas can be attributed to its possession of multiple protein-protein interaction domains, which sets it apart as a unique class of adaptor protein. It is well established that p130Cas interacts critically with the CT10 regulator of kinase (Crk) adaptor protein family members, including CrkII, CrkI, and Crk-like (CrkL), which is the basis for the naming of the Cas family. The Crk family proteins play a crucial role in integrating signals from various sources, such as growth factors, extracellular matrix molecules, bacterial pathogens, and apoptotic cells. An increasing body of evidence suggests that the dysregulation of Crk family proteins is linked to various human diseases, including cancer and increased susceptibility to pathogen infections. This review focuses primarily on the structural and functional aspects of the interaction between p130Cas and the Crk family proteins, providing insights into how these proteins regulate specific signaling events. Furthermore, we delve into the functions of p130Cas and the Crk family proteins in both normal and tumor cells to gain a comprehensive understanding of their collaborative roles in cellular physiology and pathology. This review demonstrates that tumor cell migration and invasion are the two cellular functions that have been studied the most for the p130Cas-Crk/CrkL axis. Understanding the tumor cell migration and invasion that require both p130Cas and Crk/CrkL is necessary to further evaluate the role of the p130Cas-Crk/CrkL axis in cancer. Establishing the contribution of the p130Cas-Crk/CrkL axis to cancer will facilitate the development of cancer drugs targeting the axis to inhibit cancer cell dissemination and improve patient outcomes.
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Affiliation(s)
- Pegah Farhadi
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah 67155, Iran
| | - Taeju Park
- Children’s Mercy Research Institute, Children’s Mercy Kansas City, Kansas City, MO 64108, USA
- Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA
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7
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Mierke CT. Softness or Stiffness What Contributes to Cancer and Cancer Metastasis? Cells 2025; 14:584. [PMID: 40277910 PMCID: PMC12026216 DOI: 10.3390/cells14080584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 04/08/2025] [Accepted: 04/08/2025] [Indexed: 04/26/2025] Open
Abstract
Beyond the genomic and proteomic analysis of bulk and single cancer cells, a new focus of cancer research is emerging that is based on the mechanical analysis of cancer cells. Therefore, several biophysical techniques have been developed and adapted. The characterization of cancer cells, like human cancer cell lines, started with their mechanical characterization at mostly a single timepoint. A universal hypothesis has been proposed that cancer cells need to be softer to migrate and invade tissues and subsequently metastasize in targeted organs. Thus, the softness of cancer cells has been suggested to serve as a universal physical marker for the malignancy of cancer types. However, it has turned out that there exists the opposite phenomenon, namely that stiffer cancer cells are more migratory and invasive and therefore lead to more metastases. These contradictory results question the universality of the role of softness of cancer cells in the malignant progression of cancers. Another problem is that the various biophysical techniques used can affect the mechanical properties of cancer cells, making it even more difficult to compare the results of different studies. Apart from the instrumentation, the culture and measurement conditions of the cancer cells can influence the mechanical measurements. The review highlights the main advances of the mechanical characterization of cancer cells, discusses the strength and weaknesses of the approaches, and questions whether the passive mechanical characterization of cancer cells is still state-of-the art. Besides the cell models, conditions and biophysical setups, the role of the microenvironment on the mechanical characteristics of cancer cells is presented and debated. Finally, combinatorial approaches to determine the malignant potential of tumors, such as the involvement of the ECM, the cells in a homogeneous or heterogeneous association, or biological multi-omics analyses, together with the dynamic-mechanical analysis of cancer cells, are highlighted as new frontiers of research.
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Affiliation(s)
- Claudia Tanja Mierke
- Faculty of Physics and Earth System Sciences, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, Leipzig University, 04103 Leipzig, Germany
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Saadh MJ, Bishoyi AK, Ballal S, Singh A, Kareem RA, Devi A, Sharma GC, Naidu KS, Sead FF. MicroRNAs as behind-the-scenes molecules in breast cancer metastasis and their therapeutic role through novel microRNA-based delivery strategies. Gene 2025; 944:149272. [PMID: 39894085 DOI: 10.1016/j.gene.2025.149272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 01/20/2025] [Indexed: 02/04/2025]
Abstract
Breast cancer is the primary cause of cancer-related death and the most frequent malignancy among women in Western countries. Although there have been advancements in combination treatments and targeted therapies for the metastatic diseases management, metastatic breast cancer is still the second most common cause of cancer-related deaths among U.S. women. The routes of metastasis encompass invasion, intravasation, circulation, extravasation, infiltration into a remote location to establish a metastatic niche, and the formation of micro-metastases in a new environment. Each of these processes is regulated by changes in gene expression. MicroRNAs (miRNAs) are widely expressed by a variety of organisms and have a key role in cell activities including suppressing or promoting cancer through regulating various pathways. Target gene expression is post-transcriptionally regulated by miRNAs, which contribute to the development, spread, and metastasis of breast cancer. In this study, we comprehensively discussed the role of miRNAs as predictors of breast cancer metastasis, their correlation with the spread of the disease to certain organs, and their potential application as targets for breast cancer treatment. We also provided molecular mechanisms of miRNAs in the progression of breast cancer, as well as current challenges in miRNA-based therapeutic approaches. Furthermore, as one of the primary issues with the treatment of solid malignancies is the efficient delivery of miRNAs, we examined a number of cutting-edge carriers for miRNA-based therapies and CRISPR/Cas9 as a targeted therapy for breast cancer.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman 11831, Jordan.
| | - Ashok Kumar Bishoyi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot 360003, Gujarat, India
| | - Suhas Ballal
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Abhayveer Singh
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura 140401, Punjab, India
| | | | - Anita Devi
- Department of Chemistry Chandigarh Engineering College, Chandigarh Group of Colleges-Jhanjeri, Mohali 140307, Punjab, India
| | - Girish Chandra Sharma
- Department of Applied Sciences-Chemistry, NIMS Institute of Engineering & Technology, NIMS University Rajasthan, Jaipur, India
| | - K Satyam Naidu
- Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh 531162, India
| | - Fadhil Faez Sead
- Department of Dentistry, College of Dentistry, The Islamic University, Najaf, Iraq; Department of Medical Analysis, Medical Laboratory Technique College, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
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9
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Ouyang X, Wang J, Qiu X, Hu D, Cui J. Current developments of pharmacotherapy targeting heme oxygenase 1 in cancer (Review). Int J Oncol 2025; 66:26. [PMID: 39981901 DOI: 10.3892/ijo.2025.5732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/16/2025] [Indexed: 02/22/2025] Open
Abstract
Malignant tumors are non-communicable diseases that impact human health and quality of life. Identifying and targeting the underlying genetic drivers is a challenge. Heme oxygenase-1 (HO-1), a stress-inducible enzyme also known as heat shock protein 32, plays a crucial role in maintaining cellular homeostasis. It mitigates oxidative stress-induced damage and exhibits anti-apoptotic properties. HO-1 is expressed in a wide range of malignancies and is associated with tumor growth. However, the precise role of HO-1 in tumor development remains controversial. Drugs, both naturally occurring and chemically synthesized, can inhibit tumor growth by modulating HO-1 expression in cancer cells. The present review aimed to discuss biological functions of HO-1 pharmacological therapies targeting HO-1.
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Affiliation(s)
- Xiaohu Ouyang
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Jingbo Wang
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Xiaoyuan Qiu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Desheng Hu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Jing Cui
- Health Management Center, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, Wuhan, Hubei 430015, P.R. China
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10
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Jiang S, Li C, Liu D, Zeng F, Wei W, He T, Yang W. Role, mechanisms and effects of Radix Bupleuri in anti‑breast cancer (Review). Oncol Lett 2025; 29:166. [PMID: 39963320 PMCID: PMC11831725 DOI: 10.3892/ol.2025.14912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 12/30/2024] [Indexed: 02/20/2025] Open
Abstract
The prevalence of breast cancer among women has led to a growing need for innovative anti-breast cancer medications and an in-depth investigation into their molecular mechanisms of action, both of which are essential tactics in clinical intervention. In the clinical practice of Traditional Chinese Medicine, Radix Bupleuri and its active components have shown promise as potential anti-breast cancer agents due to their ability to target multiple pathways, exhibit synergistic effects and reduce toxicity. These compounds are considered to enhance the prognosis of patients with cancer, prolong survival and combat chemotherapy resistance. The present review aimed to delve into the anti-breast cancer properties of Radix Bupleuri and its active ingredients, highlighting their mechanisms, such as inhibition of cell proliferation, promotion of apoptosis, metastasis prevention, microenvironment improvement and synergy with certain chemotherapeutic agents. These findings may provide a scientific rationale for combining Radix Bupleuri and its active components with traditional chemotherapy agents for the management of breast cancer.
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Affiliation(s)
- Shiting Jiang
- Institute for Cancer Medicine, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Chengxia Li
- Institute for Cancer Medicine, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Dan Liu
- Institute for Cancer Medicine, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Fancai Zeng
- Laboratory of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Wenli Wei
- Institute for Cancer Medicine, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Tao He
- Institute for Cancer Medicine, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
| | - Wenli Yang
- Institute for Cancer Medicine, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
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11
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Li Z, Ren H, Tan S, Su B, Wang Y, Ren W, Zhang B, Song C, Du R, Gu Y, Wu L, Li H. CircITGA7 overexpression suppresses HCC progression via miR-330/BCL11B axis regulation. Cancer Cell Int 2025; 25:121. [PMID: 40155933 PMCID: PMC11954299 DOI: 10.1186/s12935-025-03714-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 02/23/2025] [Indexed: 04/01/2025] Open
Abstract
As a kind of prevalent malignancy globally, hepatocellular carcinoma (HCC) is characterized by significant morbidity and mortality due to the difficulties in early diagnosis and limited treatment options. Circular RNAs (circRNAs) are a type of circular single-stranded RNA molecule formed by the back-splicing of the 5' end and the 3' end of linear RNA, possessing multiple biological functions. In recent years, numerous reports have demonstrated that circRNAs are potential biomarkers and therapeutic targets for HCC. In this study, we found that circITGA7 is significantly downregulated in HCC tissue compared to adjacent non-tumor tissue. Functional experiments such as CCK8, EdU, colony formation and wound healing assays proved that overexpression of circITGA7 can effectively inhibit the proliferation, migration and invasion of HCC cells. Further research found that circITGA7 can inhibit miR-330 to release BCL11B expression, thereby promoting P53 expression, blocking the cell cycle and promoting apoptosis in HCC cells. In addition, circITGA7 can impede the proliferation of HCC cells in vivo. Therefore, circITGA7 is a potential biomarker for the diagnosis of HCC development and a potential target for the treatment of HCC.
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Affiliation(s)
- Zhijie Li
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100039, China
| | - Hui Ren
- Senior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, 100039, China
| | - Shuaishuai Tan
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China
| | - Bing Su
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China
| | - Yuchen Wang
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China
| | - Wenwen Ren
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China
| | - Boyang Zhang
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China
| | - Can Song
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China
| | - Rulong Du
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China
| | - Yuchun Gu
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China.
| | - Lida Wu
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China.
| | - Hongyu Li
- Allife Medical Science and Technology Co., Ltd. Economic and Technological Development Zone, Beijing, 100176, China.
- Department of Life Science and Bioengineering, Beijing University of Technology, Beijing, 100124, China.
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12
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Zhang X, Guo Z, Li Y, Xu Y. Splicing to orchestrate cell fate. MOLECULAR THERAPY. NUCLEIC ACIDS 2025; 36:102416. [PMID: 39811494 PMCID: PMC11729663 DOI: 10.1016/j.omtn.2024.102416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Alternative splicing (AS) plays a critical role in gene expression by generating protein diversity from single genes. This review provides an overview of the role of AS in regulating cell fate, focusing on its involvement in processes such as cell proliferation, differentiation, apoptosis, and tumorigenesis. We explore how AS influences the cell cycle, particularly its impact on key stages like G1, S, and G2/M. The review also examines AS in cell differentiation, highlighting its effects on mesenchymal stem cells and neurogenesis, and how it regulates differentiation into adipocytes, osteoblasts, and chondrocytes. Additionally, we discuss the role of AS in programmed cell death, including apoptosis and pyroptosis, and its contribution to cancer progression. Importantly, targeting aberrant splicing mechanisms presents promising therapeutic opportunities for restoring normal cellular function. By synthesizing recent findings, this review provides insights into how AS governs cellular fate and offers directions for future research into splicing regulatory networks.
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Affiliation(s)
- Xurui Zhang
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, P.R. China
| | - Zhonghao Guo
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, P.R. China
| | - Yachen Li
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, P.R. China
| | - Yungang Xu
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, P.R. China
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13
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Daetwyler S, Mazloom-Farsibaf H, Zhou FY, Segal D, Sapoznik E, Chen B, Westcott JM, Brekken RA, Danuser G, Fiolka R. Imaging of cellular dynamics from a whole organism to subcellular scale with self-driving, multiscale microscopy. Nat Methods 2025; 22:569-578. [PMID: 39939720 PMCID: PMC12039951 DOI: 10.1038/s41592-025-02598-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Accepted: 01/15/2025] [Indexed: 02/14/2025]
Abstract
Most biological processes, from development to pathogenesis, span multiple time and length scales. While light-sheet fluorescence microscopy has become a fast and efficient method for imaging organisms, cells and subcellular dynamics, simultaneous observations across all these scales have remained challenging. Moreover, continuous high-resolution imaging inside living organisms has mostly been limited to a few hours, as regions of interest quickly move out of view due to sample movement and growth. Here, we present a self-driving, multiresolution light-sheet microscope platform controlled by custom Python-based software, to simultaneously observe and quantify subcellular dynamics in the context of entire organisms in vitro and in vivo over hours of imaging. We apply the platform to the study of developmental processes, cancer invasion and metastasis, and we provide quantitative multiscale analysis of immune-cancer cell interactions in zebrafish xenografts.
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Affiliation(s)
- Stephan Daetwyler
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Hanieh Mazloom-Farsibaf
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Felix Y Zhou
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Dagan Segal
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Etai Sapoznik
- Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Bingying Chen
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jill M Westcott
- Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Rolf A Brekken
- Department of Surgery and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Cancer Biology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Gaudenz Danuser
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Reto Fiolka
- Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
- Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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14
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Doodmani SM, Safari MH, Akbari M, Farahani N, Alimohammadi M, Aref AR, Tajik F, Maghsoodlou A, Daneshi S, Tabari T, Taheriazam A, Entezari M, Nabavi N, Hashemi M. Metastasis and chemoresistance in breast cancer: Crucial function of ZEB1/2 proteins. Pathol Res Pract 2025; 267:155838. [PMID: 39954369 DOI: 10.1016/j.prp.2025.155838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 12/20/2024] [Accepted: 02/10/2025] [Indexed: 02/17/2025]
Abstract
Breast cancer remains one of the leading causes of mortality worldwide. While advancements in chemotherapy, immunotherapy, radiotherapy, and targeted therapies have significantly improved breast cancer treatment, many patients are diagnosed at advanced stages, where tumor cells exhibit aggressive behavior and therapy resistance. Understanding the mechanisms driving breast cancer progression is therefore critical. Metastasis is a major factor that drastically reduces patient prognosis and survival, accounting for most breast cancer-related deaths. ZEB proteins have emerged as key regulators of cancer metastasis. Beyond their role in metastasis, ZEB proteins also influence drug resistance. This review focuses on the role of ZEB1 and ZEB2 in regulating breast cancer metastasis. These proteins interact with components of the tumor microenvironment (TME) to drive cancer progression and metastasis. Additionally, ZEB proteins regulate angiogenesis through interactions with VEGF. Targeting ZEB proteins offers potential therapeutic benefits, particularly for aggressive breast cancer subtypes such as triple-negative breast cancer (TNBC), which often show poor therapeutic response. ZEB proteins also influence the sensitivity of breast cancer cells to chemotherapy, making them promising targets for enhancing treatment efficacy. Given their upregulation in breast cancer, ZEB proteins can serve as valuable diagnostic and prognostic markers.
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Affiliation(s)
- Seyed Mohammad Doodmani
- Department of Pathobiology, Faculty of Specialized Veterinary Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mohamad Hosein Safari
- Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
| | - Mohammadarian Akbari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | - Najma Farahani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences,Tehran, Iran
| | - Amir Reza Aref
- Department of Vitro Vision, DeepkinetiX, Inc, Boston, MA, USA
| | - Fatemeh Tajik
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, USA
| | - Amin Maghsoodlou
- Young Researchers and Elite Club, Damghan Branch, Islamic Azad University, Damghan, Iran
| | - Salman Daneshi
- Department of Public Health, School of Health, Jiroft University of Medical Sciences, Jiroft, Iran
| | - Teimour Tabari
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Noushin Nabavi
- Independent Researcher, Victoria, British Columbia V8V 1P7, Canada
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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15
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Wang L, Li N, Chen Y, Qiao Y, Song Y, Zhang X, Zhao H, Ran W, Li G, Xing X. GPSM1 interacts and cooperates with MMP19 to promote proliferation and EMT in colorectal cancer cells. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2025; 1872:119903. [PMID: 39855604 DOI: 10.1016/j.bbamcr.2025.119903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 01/10/2025] [Accepted: 01/11/2025] [Indexed: 01/27/2025]
Abstract
Among patients with colorectal cancer (CRC), metastasis accounts for the majority of deaths, and epithelial-mesenchymal transition (EMT) is important in the metastatic process. However, the mechanism underlying the correlation between the two in CRC is unknown. Here, we verified that a receptor-independent protein, G-protein signaling modulator 1 (GPSM1), was increased in CRC and had a significant positive correlation with matrix metalloproteinase 19 (MMP19). GPSM1 and MMP19 knockdown or overexpression decreased and increased proliferation, migration and invasion of CRC cells, respectively. In addition, overexpression or knockdown of GPSM1 and MMP19 upregulated and inhibited EMT, respectively. Interfering with MMP19 reversed EMT activation via GPSM1 overexpression. Apoptosis was induced by GPSM1 and MMP19 knockdown and activated the caspase3/Bcl-2/Bax signaling pathway. In conclusion, these results support the role of GPSM1 and MMP19 in CRC progression.
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Affiliation(s)
- Lu Wang
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Na Li
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yang Chen
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yehua Qiao
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yaolin Song
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiangyan Zhang
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Han Zhao
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wenwen Ran
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Guangqi Li
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaoming Xing
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, China.
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16
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Ahmadi S, Yazdi F, Khastar S, Kaur I, Ahmed MH, Kumar A, Rathore G, Kaur P, Shahsavan M, Dehghani-Ghorbi M, Akhavan-Sigari R. Molecular Mechanism of lncRNAs in Regulation of Breast Cancer Metastasis; a Comprehensive Review. Cell Biochem Biophys 2025; 83:229-245. [PMID: 39367197 DOI: 10.1007/s12013-024-01535-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/07/2024] [Indexed: 10/06/2024]
Abstract
Although the number of breast cancer deaths has decreased, and there have been developments in targeted therapies and combination treatments for the management of metastatic illness, metastatic breast cancer is still the second most common cause of cancer-related deaths in U.S. women. Numerous phases and a vast number of proteins and signaling molecules are involved in the invasion-metastasis cascade. The tumor cells penetrate and enter the blood or lymphatic vessels, and travel to distant organs via the lymphatic or blood vessels. Tumor cells enter cell cycle arrest, adhere to capillary beds in the target organ, and then disseminate throughout the organ's parenchyma, proliferating and enhancing angiogenesis. Each of these processes is regulated by changes in the expression of different genes, in which lncRNAs play a role in this regulation. Transcripts that are longer than 200 nucleotides and do not translate into proteins are called RNAs. LncRNA molecules, whose function depends on their unique molecular structure, play significant roles in controlling the expression of genes at various epigenetic levels, transcription, and so on. LncRNAs have essential functions in regulating the expression of genes linked to cell development in healthy and pathological processes, specialization, programmed cell death, cell division, invasion, DNA damage, and spread to other parts of the body. A number of cancer types have been shown to exhibit aberrant expression of lncRNAs. In this review, we describe the general characteristics, potential molecular mechanisms and targeted therapy of lncRNAs and discuss the emerging functions of lncRNAs in breast cancer.
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Affiliation(s)
- Shokoufeh Ahmadi
- Department of Microbiology, Rabe'Rashidi University, Tabriz, Iran
| | - Farzaneh Yazdi
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Sahar Khastar
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Irwanjot Kaur
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka-560069, India
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan-303012, India
| | | | - Abhishek Kumar
- School of Pharmacy-Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Gangoh, Uttar Pradesh-247341, India
- Department of Pharmacy, Arka Jain University, Jamshedpur, Jharkhand-831001, India
| | - Gulshan Rathore
- Department of Pharmaceutics, NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India
| | - Parjinder Kaur
- Chandigarh Pharmacy College, Chandigarh Group of Colleges-Jhanjeri, Mohali 140307, Punjab, India
| | - Mohammad Shahsavan
- Department of Orthopedic Surgery, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Mahmoud Dehghani-Ghorbi
- Hematology-Oncology Department, Imam Hossein Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Akhavan-Sigari
- Department of Neurosurgery, University Medical Center, Tuebingen, Germany
- Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Warsaw, Poland
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17
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Chen H, Liu L, Xing G, Zhang D, A. N, Huang J, Li Y, Zhao G, Liu M. Exosome tropism and various pathways in lung cancer metastasis. Front Immunol 2025; 16:1517495. [PMID: 40028322 PMCID: PMC11868168 DOI: 10.3389/fimmu.2025.1517495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 01/20/2025] [Indexed: 03/05/2025] Open
Abstract
Lung cancer, characterized by its high morbidity and mortality rates, has the capability to metastasize to various organs, thereby amplifying its detrimental impact and fatality. The metastasis of lung cancer is a complex biological phenomenon involving numerous physiological transformations. Exosomes, small membranous vesicles enriched with biologically active components, are pivotal in mediating intercellular communication and regulating physiological functions due to their specificity and stability. Extensive research has elucidated the production and functions of exosomes in cancer contexts. Multitude of evidence demonstrates a strong association between lung cancer metastasis and exosomes. Additionally, the concept of the pre-metastatic niche is crucial in the metastatic process facilitated by exosomes. This review emphasizes the role of exosomes in mediating lung cancer metastasis and their impact on the disease's development and the progression to other tissues. Furthermore, it explores the potential of exosomes as biomarkers for lung cancer metastasis, offering significant insights for future clinical advancements.
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Affiliation(s)
- Hui Chen
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Lin Liu
- Department of Drug Dispensing, The Third Hospital of Mianyang, Sichuan Mental Health Center, MianYang, China
| | - Gang Xing
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Dan Zhang
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Niumuqie A.
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Jianlin Huang
- Department of Pharmacy, Luzhou Naxi District People’s Hospital, Luzhou, China
| | - Yaling Li
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Ge Zhao
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Minghua Liu
- School of Pharmacy, Southwest Medical University, Luzhou, China
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18
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Noguchi S, Shimonishi R. Interleukin-6 promotes the epithelial mesenchymal transition in canine tonsillar squamous cell carcinoma cells. Res Vet Sci 2025; 183:105487. [PMID: 39637476 DOI: 10.1016/j.rvsc.2024.105487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 11/10/2024] [Accepted: 11/30/2024] [Indexed: 12/07/2024]
Abstract
Canine oral squamous cell carcinoma (CoSCC) is often associated with suppurative inflammation. Metastasis of malignant tumors is one of the signs of major interest in oncology because it speaks of disease progression, where the involvement of interleukin-6 (IL-6) in cancer progression is so far unknown. Therefore, the aim of this study was the determination of the role of IL-6 in metastasis in CoSCC cells model through expression analysis of mRNA and protein using real-time PCR and western blotting and assessment of cell migration and invasion. The messenger RNA (mRNA) expression level of IL-6 was elevated in CoSCC tissues, and the IL-6 receptor protein was expressed in CoSCC cell lines. Furthermore, IL-6 levels were associated and showed negative correlation with survival time (rs = -0.92857) in dogs with tonsillar SCC. Recombinant canine IL-6 (rcIL-6) treatment promoted migration and invasion, in addition to increasing the viable cell number of the tonsillar SCC cell line (TSCCLN#6). Consistently, the protein expression of phosphorylated ERK1/2 and STAT3 and Fascin1 (FSCN1) was upregulated by treatment with rcIL-6 in a dose-dependent manner. Treatment with ERK or STAT3 inhibitors abolished the effects of rcIL-6, and the ERK inhibitor successfully downregulated the expression of FSCN1. In conclusion, IL-6 may be involved in tonsillar CoSCC invasion and metastasis through the activation of the mitogen-activated protein kinase and Janus tyrosine kinase/signal transducer and activator of transcription signaling.
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Affiliation(s)
- Shunsuke Noguchi
- Laboratory of Veterinary Radiology, Graduate School of Veterinary Science, Osaka Metropolitan University, 1-58 Rink Ourai Kita, Izumisano, Osaka 598-8531, Japan.
| | - Ryo Shimonishi
- Laboratory of Veterinary Radiology, School of Veterinary Science, Osaka Metropolitan University, 1-58 Rinku Ourai Kita, Izumisano, Osaka 598-8531, Japan
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19
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Chen XP, Yang ZT, Yang SX, Li EM, Xie L. PAK2 as a therapeutic target in cancer: Mechanisms, challenges, and future perspectives. Biochim Biophys Acta Rev Cancer 2025; 1880:189246. [PMID: 39694422 DOI: 10.1016/j.bbcan.2024.189246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 12/07/2024] [Accepted: 12/10/2024] [Indexed: 12/20/2024]
Abstract
P21-activated kinases (PAKs) are crucial regulators within cellular signaling pathways and have been implicated in a range of human diseases, including cancer. Among the PAK family, PAK2 is widely expressed across various tissues and has emerged as a significant driver of cancer progression. However, systematic studies on PAK2 remain limited. This review provides a comprehensive overview of PAK2's role in cancer, focusing on its involvement in processes such as angiogenesis, metastasis, cell survival, metabolism, immune response, and drug resistance. We also explore its function in key cancer signaling pathways and the potential of small-molecule inhibitors targeting PAK2 for therapeutic purposes. Despite promising preclinical data, no PAK2 inhibitors have reached clinical practice, underscoring challenges related to their specificity and therapeutic application. This review highlights the biological significance of PAK2 in cancer and its interactions with critical signaling pathways, offering valuable insights for future research. We also discuss the major obstacles in developing PAK inhibitors and propose strategies to overcome these barriers, paving the way for their clinical translation.
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Affiliation(s)
- Xin-Pan Chen
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Zi-Tao Yang
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Shang-Xin Yang
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - En-Min Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; The Laboratory for Cancer Molecular Biology, Shantou Academy Medical Sciences, Shantou 515041, Guangdong, China; Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Shantou 515041, Guangdong, China.
| | - Lei Xie
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China.
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20
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Sancho-Albero M, Decio A, Akpinar R, De Luigi A, Giavazzi R, Terracciano LM, De Cola L. Melanoma extracellular vesicles membrane coated nanoparticles as targeted delivery carriers for tumor and lungs. Mater Today Bio 2025; 30:101433. [PMID: 39866783 PMCID: PMC11764275 DOI: 10.1016/j.mtbio.2024.101433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/17/2024] [Accepted: 12/27/2024] [Indexed: 01/28/2025] Open
Abstract
Targeting is the most challenging problem to solve for drug delivery systems. Despite the use of targeting units such as antibodies, peptides and proteins to increase their penetration in tumors the amount of therapeutics that reach the target is very small, even with the use of nanoparticles (NPs). Nature has solved the selectivity problem using a combination of proteins and lipids that are exposed on the cell membranes and are able to recognize specific tissues as demonstrated by cancer metastasis. Extracellular vesicles (EVs) have a similar ability in target only certain organs or to return to their original cells, showing home behavior. Here we report a strategy inspired by nature, using a combination of NPs and the targeting cell membranes of EVs. We implement the EV membranes, extracted by the EVs produced by melanoma B16-BL6 cells, as a coating of organosilica porous particles with the aim of targeting tumors and lung metastasis, while avoiding systemic effects and accumulation of the NPs in undesired organs. The tissue-specific fingerprint provided by the EVs-derived membranes from melanoma cells provides preferential uptake into the tumor and selective targeting of lungs. The ability of the EVs hybrid systems to behave as the natural EVs was demonstrated in vitro and in vivo in two different tumor models. As a proof of concept, the loading and release of doxorubicin, was investigated and its accumulation demonstrated in the expected tissues.
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Affiliation(s)
- María Sancho-Albero
- Department of Biochemistry and Molecular Pharmacology. Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan, Italy
| | - Alessandra Decio
- Department of Oncology. Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan, Italy
| | - Reha Akpinar
- IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy
| | - Ada De Luigi
- Department of Biochemistry and Molecular Pharmacology. Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan, Italy
| | - Raffaella Giavazzi
- Department of Oncology. Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan, Italy
| | - Luigi M. Terracciano
- IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, 20089, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy
| | - Luisa De Cola
- Department of Biochemistry and Molecular Pharmacology. Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Via Mario Negri, 2, Milan, Italy
- Department of Pharmaceutical Science, DISFARM. Università degli Studi di Milano, Milan, 20133, Italy
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21
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Bowley TY, Ortiz MC, Lagutina IV, Steinkamp MP, Fahy BN, Tawfik B, Harari-Turquie M, Marchetti D. A Melanoma Brain Metastasis CTC Signature and CTC:B-cell Clusters Associate with Secondary Liver Metastasis: A Melanoma Brain-Liver Metastasis Axis. CANCER RESEARCH COMMUNICATIONS 2025; 5:295-308. [PMID: 39831781 PMCID: PMC11816052 DOI: 10.1158/2767-9764.crc-24-0498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/20/2024] [Accepted: 01/15/2025] [Indexed: 01/22/2025]
Abstract
SIGNIFICANCE This study provides important insights into the relevance of prometastatic CTC:B-cell clusters in melanoma progression, extends the importance of the CTC RPL/RPS gene signature beyond primary metastasis/melanoma brain metastasis driving targeted organ specificity for liver metastasis ("metastasis of metastasis"), and identifies new targets for clinical melanoma metastasis therapies.
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Affiliation(s)
- Tetiana Y. Bowley
- Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
| | - Mireya C. Ortiz
- Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
| | - Irina V. Lagutina
- Animal Models Shared Resource, The University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico
| | - Mara P. Steinkamp
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
| | - Bridget N. Fahy
- Division of Surgical Oncology and Palliative Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico
| | - Bernard Tawfik
- Division of Hematology and Oncology, Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico
| | - Moises Harari-Turquie
- Division of Hematology and Oncology, Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico
| | - Dario Marchetti
- Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
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22
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Miranda I, Jahan N, Shevde LA. The metastatic cascade through the lens of therapeutic inhibition. Cell Rep Med 2025; 6:101872. [PMID: 39706193 PMCID: PMC11866422 DOI: 10.1016/j.xcrm.2024.101872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 10/21/2024] [Accepted: 11/18/2024] [Indexed: 12/23/2024]
Abstract
Metastasis is a main cause of cancer-related death, and a deeper understanding of the metastatic process will inform more targeted and mechanistic approaches that can abrogate challenges in treatment efficacy and toxicity. Several steps throughout the metastatic cascade, from angiogenesis to secondary tumor formation, offer specific vulnerabilities to therapies that can lead to the decline or cessation of metastatic progression. A deeper understanding of the metastatic cascade also allows combination systemic therapies to be used synergistically. In this review, we describe current treatment modalities in the context of multiple steps of the metastatic cascade. We highlight their mechanisms and present their efficacy across multiple cancers. This work also presents targets within the metastatic cascade in need of more research that can advance the landscape of treatments and lead to the goal of metastatic cancer remission.
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Affiliation(s)
- Ian Miranda
- Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Nusrat Jahan
- Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Lalita A Shevde
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
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23
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Jin C, Lu Z, Chen Y, Hu H, Zhou M, Zhang Y, Ouyang G, Li T, Sheng L. Identification of biomarkers for chronic lymphocytic leukemia risk: a proteome-wide Mendelian randomization study. Discov Oncol 2025; 16:2. [PMID: 39751938 PMCID: PMC11699013 DOI: 10.1007/s12672-024-01699-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 12/11/2024] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy. Although previous research has explored associations between plasma proteins and CLL, the causal relationships remain unclear. This study used Mendelian randomization (MR) to investigate the causal relationship between 7156 plasma proteins and CLL risk. METHODS A two-sample MR analysis assessed the impact of specific plasma proteins on CLL risk, using data from the Finngen Proteomics project (analyzing 828 participants) and the UK Biobank. Additional analyses included colocalization, phenomenon-wide MR, and protein-protein interaction networks. RESULTS The study identified nine plasma proteins significantly associated with CLL risk. Increased levels of Peptidyl-prolyl cis-trans isomerase E (PPIE) (OR = 1.66, 95% CI 1.22-2.27, P = 0.001) were associated with an increased risk of developing CLL, whereas Protein O-Mannosyltransferase 2 (POMGNT2) (OR = 0.62, 95% CI 0.41-0.91, P = 0.017) and C-C Motif Chemokine Ligand 14(CCL14) (OR = 0.80, 95% CI 0.67-0.94, P = 0.010) were associated with a reduced risk of CLL. Colocalization analysis suggested that PPIE may share pathogenic variants with CLL (PP.H4 = 0.758). Phenomenon-wide MR analysis of PPIE also indicated associations with other clinical features, including rheumatic diseases and type 2 diabetes. Protein-protein interaction and drug-gene interaction analyses highlighted CDC5L and SNW1 as potential therapeutic targets. CONCLUSION This study identifies nine plasma proteins linked to CLL risk, with PPIE offering new insights into the disease's pathogenesis. Further research is needed to validate these findings and explore their potential as therapeutic targets.
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Affiliation(s)
- Changyu Jin
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China
| | - Zehong Lu
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China
| | - Yuzhan Chen
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China
| | - Huijie Hu
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China
| | - Miao Zhou
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China
| | - Yanli Zhang
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China
| | - Guifang Ouyang
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China.
| | - Tongyu Li
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China.
| | - Lixia Sheng
- Department of Hematology, The First Affiliated Hospital of Ningbo University, No.59 Liu-Ting Road, Ningbo, 315000, People's Republic of China.
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24
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Wu Y, Shang J, Zhang X, Li N. Advances in molecular imaging and targeted therapeutics for lymph node metastasis in cancer: a comprehensive review. J Nanobiotechnology 2024; 22:783. [PMID: 39702277 PMCID: PMC11657939 DOI: 10.1186/s12951-024-02940-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 10/19/2024] [Indexed: 12/21/2024] Open
Abstract
Lymph node metastasis is a critical indicator of cancer progression, profoundly affecting diagnosis, staging, and treatment decisions. This review article delves into the recent advancements in molecular imaging techniques for lymph nodes, which are pivotal for the early detection and staging of cancer. It provides detailed insights into how these techniques are used to visualize and quantify metastatic cancer cells, resident immune cells, and other molecular markers within lymph nodes. Furthermore, the review highlights the development of innovative, lymph node-targeted therapeutic strategies, which represent a significant shift towards more precise and effective cancer treatments. By examining cutting-edge research and emerging technologies, this review offers a comprehensive overview of the current and potential impact of lymph node-centric approaches on cancer diagnosis, staging, and therapy. Through its exploration of these topics, the review aims to illuminate the increasingly sophisticated landscape of cancer management strategies focused on lymph node assessment and intervention.
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Affiliation(s)
- Yunhao Wu
- Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Jin Shang
- Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Xinyue Zhang
- The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China
| | - Nu Li
- The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
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25
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Qi D, Zhang H, Xiong F, Zhang G, Tao B, Wang C. Renal cell carcinoma and macrophage research: A bibliometric analysis (2004-2023). Medicine (Baltimore) 2024; 103:e40954. [PMID: 39686418 PMCID: PMC11651438 DOI: 10.1097/md.0000000000040954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
To analyze hotspots and trends in renal cell carcinoma (RCC)-macrophage research using bibliometric analysis, although numerous studies on macrophages in RCC have been recently reported, understanding the progressive trends in this field remains challenging. Publications focused on macrophages in RCC were extracted from the Web of Science Core Collection. VOSviewer, Citespace, and Bibliometrics online platforms were used to visualize hot topics and global trends in RCC-macrophage research. In total, 778 papers were collected. China produced the most articles; however, the United States accounted for the largest number of citations. Oncology journals published the most articles, and these were cited most frequently. Based on keyword analysis, "prognosis," "immunotherapy," "tumor microenvironment," and "immune infiltration" represented the primary research hotspots. In summary, RCC-macrophage studies have emerged as a key research focus; particularly, incorporating multiomics data and applying artificial intelligence for predictive modeling have demonstrated significant potential. Our study suggests that the resistance mechanism of immune checkpoint inhibitors and the interaction between macrophages and immune checkpoint inhibitors will be pivotal areas for future research.
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Affiliation(s)
- Dingtian Qi
- Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Haoxun Zhang
- Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Feng Xiong
- Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Guoling Zhang
- Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Boju Tao
- Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chunyang Wang
- Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
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26
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Guo J, Wang J, Fan S, Gao M, Liu G, Xia Y. The Novel Elemene Derivative, OMe-Ph-Elemene, Attenuates Oxidative Phosphorylation and Facilitates Apoptosis by Inducing Intracellular Reactive Oxygen Species. Antioxidants (Basel) 2024; 13:1499. [PMID: 39765827 PMCID: PMC11672920 DOI: 10.3390/antiox13121499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 12/01/2024] [Accepted: 12/05/2024] [Indexed: 01/11/2025] Open
Abstract
The incidence and mortality rates of colorectal cancer have been steadily increasing, making it one of the most prevalent cancers globally. Although current chemotherapy drugs have shown some efficacy in treating this disease, their associated side effects necessitate the development of more effective treatments and medications. The clinical application of elemene is widely utilized in tumor treatment; however, its efficacy is hindered by the requirement for high dosage and suboptimal anticancer effects. Thus, we have made modifications and enhancements to elemene, resulting in the development of a novel compound named (E)-8-(3,4,5-OMe-Ph)-β-Elemene (abbreviated as OMe-Ph-Elemene) that demonstrates significantly enhanced efficacy in suppressing colorectal cancer. We conducted an in vivo study and demonstrated the potential of OMe-Ph-Elemene in suppressing the growth of colorectal cancer xenograft tumors in zebrafish. The in vitro experiments revealed that OMe-Ph-Elemene effectively inhibited the proliferation and migration of colorectal cancer SW480 and HT-29 cells by inducing reactive oxygen species (ROS)-caused apoptosis and inhibiting mitochondrial oxidative phosphorylation. The mechanism was elucidated through high-throughput proteomic analysis and molecular biological analysis, revealing that OMe-Ph-Elemene induced cellular oxidative stress by downregulating CISD3 and promoted cell apoptosis by downregulating TRIAP1 and upregulating HMOX1. Furthermore, OMe-Ph-Elemene suppressed colorectal cancer cells' mitochondrial oxidative phosphorylation by downregulating NDUFA7. In summary, the utilization of the elemene parent nucleus structure has led to the derivation of a novel tumor suppressor compound characterized by high efficacy and low toxicity, thereby providing a significant reference for the development of innovative drugs for colorectal cancer treatment.
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Affiliation(s)
- Jianhua Guo
- Cheeloo College of Medicine, Shandong University, Jinan 250012, China;
- Key Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, College of Medical Engineering, Jining Medical University, Jining 272067, China; (J.W.); (S.F.); (M.G.)
| | - Jiayi Wang
- Key Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, College of Medical Engineering, Jining Medical University, Jining 272067, China; (J.W.); (S.F.); (M.G.)
| | - Shuhao Fan
- Key Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, College of Medical Engineering, Jining Medical University, Jining 272067, China; (J.W.); (S.F.); (M.G.)
| | - Mucong Gao
- Key Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, College of Medical Engineering, Jining Medical University, Jining 272067, China; (J.W.); (S.F.); (M.G.)
| | - Guodu Liu
- Inner Mongolia Key Laboratory of Fine Organic Synthesis, College of Chemistry and Chemical Engineering, Inner Mongolia University (South Campus), Hohhot 010030, China
| | - Yong Xia
- Cheeloo College of Medicine, Shandong University, Jinan 250012, China;
- Key Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, College of Medical Engineering, Jining Medical University, Jining 272067, China; (J.W.); (S.F.); (M.G.)
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27
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Liaghat M, Ferdousmakan S, Mortazavi SH, Yahyazadeh S, Irani A, Banihashemi S, Seyedi Asl FS, Akbari A, Farzam F, Aziziyan F, Bakhtiyari M, Arghavani MJ, Zalpoor H, Nabi-Afjadi M. The impact of epithelial-mesenchymal transition (EMT) induced by metabolic processes and intracellular signaling pathways on chemo-resistance, metastasis, and recurrence in solid tumors. Cell Commun Signal 2024; 22:575. [PMID: 39623377 PMCID: PMC11610171 DOI: 10.1186/s12964-024-01957-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 11/22/2024] [Indexed: 12/06/2024] Open
Abstract
The intricate cellular process, known as the epithelial-mesenchymal transition (EMT), significantly influences solid tumors development. Changes in cell shape, metabolism, and gene expression linked to EMT facilitate tumor cell invasion, metastasis, drug resistance, and recurrence. So, a better understanding of the intricate processes underlying EMT and its role in tumor growth may lead to the development of novel therapeutic approaches for the treatment of solid tumors. This review article focuses on the signals that promote EMT and metabolism, the intracellular signaling pathways leading to EMT, and the network of interactions between EMT and cancer cell metabolism. Furthermore, the functions of EMT in treatment resistance, recurrence, and metastasis of solid cancers are covered. Lastly, treatment approaches that focus on intracellular signaling networks and metabolic alterations brought on by EMT will be discussed.
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Affiliation(s)
- Mahsa Liaghat
- Department of Medical Laboratory Sciences, Faculty of Medical Sciences, Kazerun Branch, Islamic Azad University, Kazerun, Iran
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
| | - Saeid Ferdousmakan
- Department of Pharmacy Practice, Nargund College of Pharmacy, Bangalore, 560085, India
| | | | - Sheida Yahyazadeh
- Department of Immunology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Asrin Irani
- Department of Biology, Faculty of Basic Sciences, University of Guilan, Rasht, Iran
| | - Sara Banihashemi
- Department of Bioscience, School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | | | - Abdullatif Akbari
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farnoosh Farzam
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Fatemeh Aziziyan
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Maryam Bakhtiyari
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Mohammad Javad Arghavani
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran
| | - Hamidreza Zalpoor
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran.
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
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28
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Sui L, Wang J, Jiang WG, Song X, Ye L. Molecular mechanism of bone metastasis in breast cancer. Front Oncol 2024; 14:1401113. [PMID: 39605887 PMCID: PMC11599183 DOI: 10.3389/fonc.2024.1401113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 10/24/2024] [Indexed: 11/29/2024] Open
Abstract
Bone metastasis is a debilitating complication that frequently occurs in the advanced stages of breast cancer. However, the underlying molecular and cellular mechanisms of the bone metastasis remain unclear. Here, we elucidate how bone metastasis arises from tumor cells that detach from the primary lesions and infiltrate into the surrounding tissue, as well as how these cells disseminate to distant sites. Specifically, we elaborate how tumor cells preferentially grow within the bone micro-environment and interact with bone cells to facilitate bone destruction, characterized as osteoclastic bone metastasis, as well as new bone matrix deposition, characterized as osteoblastic bone metastasis. We also updated the current understanding of the molecular mechanisms underlying bone metastasis and reasons for relapse in breast cancer, and also opportunities of developing novel diagnostic approaches and treatment.
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Affiliation(s)
- Laijian Sui
- Department of Orthopedics, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China
- Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, United Kingdom
| | - Jing Wang
- Department of Intensive Care Unit, Yantai Yuhuangding Hospital, Yantai, Shandong, China
| | - Wen G. Jiang
- Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, United Kingdom
| | - Xicheng Song
- Department of Otorhinolaryngol and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, China
| | - Lin Ye
- Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, United Kingdom
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29
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Chen A, Huang H, Fang S, Hang Q. ROS: A "booster" for chronic inflammation and tumor metastasis. Biochim Biophys Acta Rev Cancer 2024; 1879:189175. [PMID: 39218404 DOI: 10.1016/j.bbcan.2024.189175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 08/22/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Reactive oxygen species (ROS) are a group of highly active molecules produced by normal cellular metabolism and play a crucial role in the human body. In recent years, researchers have increasingly discovered that ROS plays a vital role in the progression of chronic inflammation and tumor metastasis. The inflammatory tumor microenvironment established by chronic inflammation can induce ROS production through inflammatory cells. ROS can then directly damage DNA or indirectly activate cellular signaling pathways to promote tumor metastasis and development, including breast cancer, lung cancer, liver cancer, colorectal cancer, and so on. This review aims to elucidate the relationship between ROS, chronic inflammation, and tumor metastasis, explaining how chronic inflammation can induce tumor metastasis and how ROS can contribute to the evolution of chronic inflammation toward tumor metastasis. Interestingly, ROS can have a "double-edged sword" effect, promoting tumor metastasis in some cases and inhibiting it in others. This article also highlights the potential applications of ROS in inhibiting tumor metastasis and enhancing the precision of tumor-targeted therapy. Combining ROS with nanomaterials strategies may be a promising approach to enhance the efficacy of tumor treatment.
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Affiliation(s)
- Anqi Chen
- Medical College, Yangzhou University, Yangzhou 225009, China
| | - Haifeng Huang
- Department of Laboratory Medicine, The First People's Hospital of Yancheng, Yancheng 224006, China; Department of Laboratory Medicine, Yancheng Clinical Medical College of Jiangsu University, Yancheng 224006, China
| | - Sumeng Fang
- School of Mathematics, Tianjin University, Tianjin 300350, China
| | - Qinglei Hang
- Jiangsu Provincial Innovation and Practice Base for Postdoctors, Suining People's Hospital, Affiliated Hospital of Xuzhou Medical University, Suining 221200, China; Key Laboratory of Jiangsu Province University for Nucleic Acid & Cell Fate Manipulation, Yangzhou University, Yangzhou 225009, China; Department of Laboratory Medicine, Medical College, Yangzhou University, Yangzhou 225009, China.
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30
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Patni H, Chaudhary R, Kumar A. Unleashing nanotechnology to redefine tumor-associated macrophage dynamics and non-coding RNA crosstalk in breast cancer. NANOSCALE 2024; 16:18274-18294. [PMID: 39292162 DOI: 10.1039/d4nr02795g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Breast cancer is a significant global health issue. Tumor-associated macrophages (TAMs) are crucial in influencing the tumor microenvironment and the progression of the disease. TAMs exhibit remarkable plasticity in adopting distinct phenotypes ranging from pro-inflammatory and anti-tumorigenic (M1-like) to immunosuppressive and tumor-promoting (M2-like). This review elucidates the multifaceted roles of TAMs in driving breast tumor growth, angiogenesis, invasion, and metastatic dissemination. Significantly, it highlights the intricate crosstalk between TAMs and non-coding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, as a crucial regulatory mechanism modulating TAM polarization and functional dynamics that present potential therapeutic targets. Nanotechnology-based strategies are explored as a promising approach to reprogramming TAMs toward an anti-tumor phenotype. Various nanoparticle delivery systems have shown potential for modulating TAM polarization and inhibiting tumor-promoting effects. Notably, nanoparticles can deliver ncRNA therapeutics to TAMs, offering unique opportunities to modulate their polarization and activity.
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Affiliation(s)
- Hardik Patni
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad 380009, Gujarat, India.
| | - Ramesh Chaudhary
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad 380009, Gujarat, India.
| | - Ashutosh Kumar
- Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Central Campus, Navrangpura, Ahmedabad 380009, Gujarat, India.
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Zhu E, Xie Q, Huang X, Zhang Z. Application of spatial omics in gastric cancer. Pathol Res Pract 2024; 262:155503. [PMID: 39128411 DOI: 10.1016/j.prp.2024.155503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 07/25/2024] [Accepted: 07/27/2024] [Indexed: 08/13/2024]
Abstract
Gastric cancer (GC), a globally prevalent and lethal malignancy, continues to be a key research focus. However, due to its considerable heterogeneity and complex pathogenesis, the treatment and diagnosis of gastric cancer still face significant challenges. With the rapid development of spatial omics technology, which provides insights into the spatial information within tumor tissues, it has emerged as a significant tool in gastric cancer research. This technology affords new insights into the pathology and molecular biology of gastric cancer for scientists. This review discusses recent advances in spatial omics technology for gastric cancer research, highlighting its applications in the tumor microenvironment (TME), tumor heterogeneity, tumor genesis and development mechanisms, and the identification of potential biomarkers and therapeutic targets. Moreover, this article highlights spatial omics' potential in precision medicine and summarizes existing challenges and future directions. It anticipates spatial omics' continuing impact on gastric cancer research, aiming to improve diagnostic and therapeutic approaches for patients. With this review, we aim to offer a comprehensive overview to scientists and clinicians in gastric cancer research, motivating further exploration and utilization of spatial omics technology. Our goal is to improve patient outcomes, including survival rates and quality of life.
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Affiliation(s)
- Erran Zhu
- Department of Clinical Medicine, Grade 20, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, China
| | - Qi Xie
- Department of Clinical Medicine, Grade 20, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, China
| | - Xinqi Huang
- Excellent Class, Clinical Medicine, Grade 20, Hengyang Medical College, University of South China, Hengyang, Hunan, 421001, China
| | - Zhiwei Zhang
- Cancer Research Institute of Hengyang Medical College, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan; Department of Pathology, Department of Pathology of Hengyang Medical College, University of South China; The First Affiliated Hospital of University of South China, China.
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32
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Shi Y, Liu Z, Ma M, Zhao G, Zhu Y, Wang J, Yu Y, Huang X, Ye J, Li F, Wang X, Xu Q, Yin X. Platelet-Derived Growth Factor C Facilitates Malignant Behavior of Pancreatic Ductal Adenocarcinoma by Regulating SREBP1 Mediated Lipid Metabolism. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2407069. [PMID: 39225567 PMCID: PMC11516052 DOI: 10.1002/advs.202407069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 08/05/2024] [Indexed: 09/04/2024]
Abstract
Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet-derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element-binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC-mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC-induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes.
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Affiliation(s)
- Yin‐Hao Shi
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Zhi‐De Liu
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Ming‐Jian Ma
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Guang‐Yin Zhao
- Animal Experiment Center of the First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Ying‐Qin Zhu
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Jie‐Qin Wang
- Department of Pediatric SurgeryGuangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou510623China
| | - Yang‐Yin‐Hui Yu
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Xi‐Tai Huang
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Jing‐Yuan Ye
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Fu‐Xi Li
- Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou510080China
| | - Xi‐Yu Wang
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Qiong‐Cong Xu
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
| | - Xiao‐Yu Yin
- Department of Pancreato‐Biliary Surgerythe First Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou510080China
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Wang Y, Ding G, Chu C, Cheng XD, Qin JJ. Genomic biology and therapeutic strategies of liver metastasis from gastric cancer. Crit Rev Oncol Hematol 2024; 202:104470. [PMID: 39111457 DOI: 10.1016/j.critrevonc.2024.104470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 08/12/2024] Open
Abstract
The liver is a frequent site of metastasis in advanced gastric cancer (GC). Despite significant advancements in diagnostic and therapeutic techniques, the overall survival rate for patients afflicted with gastric cancer liver metastasis (GCLM) remains dismally low. Precision oncology has made significant progress in identifying therapeutic targets and enhancing our understanding of metastasis mechanisms through genome sequencing and molecular characterization. Therefore, it is crucial to have a comprehensive understanding of the various molecular processes involved in GCLM and the fundamental principles of systemic therapy to develop new treatment approaches. This paper aims to review recent findings on the diagnosis, potential biomarkers, and therapies targeting the multiple molecular processes of GCLM, with the goal of improving treatment strategies for patients with GCLM.
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Affiliation(s)
- Yichao Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 313200, China; Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China
| | - Guangyu Ding
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China
| | - Chu Chu
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 313200, China
| | - Xiang-Dong Cheng
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, China.
| | - Jiang-Jiang Qin
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou 310022, China; Key Laboratory for Molecular Medicine and Chinese Medicine Preparations, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.
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Diskul-Na-Ayudthaya P, Bae SJ, Bae YU, Van NT, Kim W, Ryu S. ANKRD1 Promotes Breast Cancer Metastasis by Activating NF- κB-MAGE-A6 Pathway. Cancers (Basel) 2024; 16:3306. [PMID: 39409926 PMCID: PMC11476229 DOI: 10.3390/cancers16193306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 09/24/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
Early detection and surgical excision of tumors have helped improve the survival rate of patients with breast cancer. However, patients with metastatic cancer typically have a poor prognosis. In this study, we propose that ANKRD1 promotes metastasis of breast cancer. ANKRD1 was found to be highly expressed in the MDA-MB-231 and MDA-LM-2 highly metastatic breast cancer cell lines compared to the non-metastatic breast cancer cell lines (MCF-7, ZR-75-30, T47D) and normal breast cancer cells (MCF-10A). Furthermore, high-grade tumors showed increased levels of ANKRD1 compared to low-grade tumors. Both in vitro and in vivo functional studies demonstrated the essential role of ANKRD1 in cancer cell migration and invasion. The previous studies have suggested a significant role of NF-κB and MAGE-A6 in breast cancer metastasis, but the upstream regulators of this axis are not well characterized. Our study suggests that ANKRD1 promotes metastasis of breast cancer by activating NF-κB as well as MAGE-A6 signaling. Our findings show that ANKRD1 is a potential therapeutic target and a diagnostic marker for breast cancer metastasis.
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Affiliation(s)
- Penchatr Diskul-Na-Ayudthaya
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
- Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand
| | - Seon Joo Bae
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
| | - Yun-Ui Bae
- Precision Medicine Lung Cancer Center, Konkuk University Medical Center, Konkuk University, Seoul 05030, Republic of Korea;
| | - Ngu Trinh Van
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
| | - Wootae Kim
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
| | - Seongho Ryu
- Soonchunhyang Institute of Medi-bio Science (SIMS), Department of Integrated Biomedical Sciences, Soonchunhyang University, Asan-si 31151, Republic of Korea; (P.D.-N.-A.); (S.J.B.); (N.T.V.)
- Department of Pathology, College of Medicine, Soonchunhyang University, Asan-si 311151, Republic of Korea
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35
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Zhao J, Zhong J, Chen Y, Chen Z, Yin H, He Y, Chen R, Guo R. Molecular features of NSCLC patients with liver metastasis. Ther Adv Med Oncol 2024; 16:17588359241275421. [PMID: 39346119 PMCID: PMC11437564 DOI: 10.1177/17588359241275421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 07/30/2024] [Indexed: 10/01/2024] Open
Abstract
Background Metastasis is the primary cause of lung cancer-related death. Primary cancer cells invade through the lymphatic or blood vessels to distant sites. Recently, it was proposed that lymphatic metastasis was more a hallmark of tumor aggressiveness or metastatic potential than a gateway to metastases. Therefore, the underlying molecular mechanism of metastasis is not entirely clear. Objectives This study aimed to explore the genetic mechanisms underlying liver metastases from lung cancer and to evaluate the efficacy of different therapies in these patients. Design We retrospectively analyzed the mutation spectrum of different biopsy samples including primary lung tumors, liver, lymph node metastasis, and circulating tumor DNA (ctDNA) from 1090 non-small-cell lung cancer (NSCLC) patients with liver metastasis between the years 2017 and 2022. Methods Demographic and disease characteristics were summarized using descriptive parameters. Time to treatment discontinuation was used to analyze the clinical outcome. Results More liquid biopsies were performed than tissue biopsies, especially in the treated advanced NSCLC patients. Liver metastasis before treatment was associated with poor response to immune checkpoint inhibitors and targeted therapy. Liver and lymph node metastasis had higher levels of single nucleotide variants and copy number variants than primary lung tumors. In paired lung and liver, lymph nodes, and simultaneous ctDNA, we found actionable mutations were always shared, while metastasis samples had multiple private mutations. Serial ctDNA analysis identifies potential resistant mutations and describes the evolution of tumor cells. Conclusion Liver and lymph node metastasis in NSCLC showed shared actionable mutations. Of note, the discrepancy of private mutations in liver and lymph node metastases indicated that liver metastases are mainly seeded by the primary tumor rather than the earlier colonized lymph node metastases.
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Affiliation(s)
- Jun Zhao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jia Zhong
- CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center
- National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, China
| | - Yujie Chen
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Zipei Chen
- Medical Oncology Department 1, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Huan Yin
- Geneplus-Beijing, Beijing, China
| | | | - Rongrong Chen
- Geneplus-Beijing, 7 Science Road, Zhongguancun Life Science Park, Changping, Beijing 102206, China
| | - Renhua Guo
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China
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36
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Cui J, Lin L, Hao F, Shi Z, Gao Y, Yang T, Yang C, Wu X, Gao R, Ru Y, Li F, Xiao C, Gao Y, Wang Y. Comprehensive review of the traditional uses and the potential benefits of epimedium folium. Front Pharmacol 2024; 15:1415265. [PMID: 39323630 PMCID: PMC11422139 DOI: 10.3389/fphar.2024.1415265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 08/20/2024] [Indexed: 09/27/2024] Open
Abstract
Epimedium Folium has been extensively utilized for medicinal purposes in China for a significant period. This review undertakes a comprehensive examination of literature pertaining to Epimedium and its metabolites over the past decade, drawing from databases such as PubMed. Through meticulous organization and synthesis of pertinent research findings, including disease models, pharmacological effects, and related aspects, this narrative review sheds light on the principal pharmacological activities and associated mechanisms of Epimedium in safeguarding the reproductive system, promoting bone health, mitigating inflammation, and combating tumors and viral infections. Consequently, this review contributes to a more profound comprehension of the recent advances in Epimedium research.
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Affiliation(s)
- Jialu Cui
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lin Lin
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Feiran Hao
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Zhuo Shi
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Yehui Gao
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Tingyu Yang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chunqi Yang
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Xiangjun Wu
- School of Pharmacy, Henan University, Kaifeng, China
| | - Rong Gao
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yi Ru
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Fangyang Li
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
| | - Chengrong Xiao
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Yue Gao
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
| | - Yuguang Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
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37
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Reeves MQ. Mapping the transcriptional evolution of human metastatic breast cancer. J Clin Invest 2024; 134:e183971. [PMID: 39225091 PMCID: PMC11364401 DOI: 10.1172/jci183971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024] Open
Abstract
Many aspects of breast cancer metastasis remain poorly understood, despite its clinical importance. In this issue of the JCI, Winkler et al. have applied an elegant patient-derived xenograft (PDX) model to map the transcriptomes of single cells in matched primary tumors and lung metastases across 13 breast cancer PDX models. They identified distinct transcriptional changes associated with metastatic evolution in lowly and highly metastatic primary tumors. Furthermore, by classifying the "epithelial-mesenchymal plasticity" (EMP) state of single cells, they revealed that considerable EMP heterogeneity exists among primary and metastatic human breast cancer cells. However, the EMP profile of a tumor does not change substantially upon metastasis. These findings give an unprecedentedly detailed view into the transcriptional heterogeneity and evolution of metastatic human breast cancer.
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Affiliation(s)
- Melissa Q. Reeves
- Huntsman Cancer Institute, and
- Department of Pathology, University of Utah, Salt Lake City, Utah, USA
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38
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Zhuang T, Wang S, Yu X, He X, Guo H, Ou C. Current status and future perspectives of platelet-derived extracellular vesicles in cancer diagnosis and treatment. Biomark Res 2024; 12:88. [PMID: 39183323 PMCID: PMC11346179 DOI: 10.1186/s40364-024-00639-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 08/12/2024] [Indexed: 08/27/2024] Open
Abstract
Platelets are a significant component of the cell population in the tumour microenvironment (TME). Platelets influence other immune cells and perform cross-talk with tumour cells, playing an important role in tumour development. Extracellular vesicles (EVs) are small membrane vesicles released from the cells into the TME. They can transfer biological information, including proteins, nucleic acids, and metabolites, from secretory cells to target receptor cells. This process affects the progression of various human diseases, particularly cancer. In recent years, several studies have demonstrated that platelet-derived extracellular vesicles (PEVs) can help regulate the malignant biological behaviours of tumours, including malignant proliferation, resistance to cell death, invasion and metastasis, metabolic reprogramming, immunity, and angiogenesis. Consequently, PEVs have been identified as key regulators of tumour progression. Therefore, targeting PEVs is a potential strategy for tumour treatment. Furthermore, the extensive use of nanomaterials in medical research has indicated that engineered PEVs are ideal delivery systems for therapeutic drugs. Recent studies have demonstrated that PEV engineering technologies play a pivotal role in the treatment of tumours by combining photothermal therapy, immunotherapy, and chemotherapy. In addition, aberrant changes in PEVs are closely associated with the clinicopathological features of patients with tumours, which may serve as liquid biopsy markers for early diagnosis, monitoring disease progression, and the prognostic assessment of patients with tumours. A comprehensive investigation into the role and potential mechanisms of PEVs in tumourigenesis may provide novel diagnostic biomarkers and potential therapeutic strategies for treating human tumours.
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Affiliation(s)
- Tongtao Zhuang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Shenrong Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xiaoqian Yu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xiaoyun He
- Departments of Ultrasound Imaging, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Hongbin Guo
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
| | - Chunlin Ou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Wang C, Xu S, Yang X. Hypoxia-Driven Changes in Tumor Microenvironment: Insights into Exosome-Mediated Cell Interactions. Int J Nanomedicine 2024; 19:8211-8236. [PMID: 39157736 PMCID: PMC11328847 DOI: 10.2147/ijn.s479533] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/06/2024] [Indexed: 08/20/2024] Open
Abstract
Hypoxia, as a prominent feature of the tumor microenvironment, has a profound impact on the multicomponent changes within this environment. Under hypoxic conditions, the malignant phenotype of tumor cells, the variety of cell types within the tumor microenvironment, as well as intercellular communication and material exchange, undergo complex alterations. These changes provide significant prospects for exploring the mechanisms of tumor development under different microenvironmental conditions and for devising therapeutic strategies. Exosomes secreted by tumor cells and stromal cells are integral components of the tumor microenvironment, serving as crucial mediators of intercellular communication and material exchange, and have consequently garnered increasing attention from researchers. This review focuses on the mechanisms by which hypoxic conditions promote the release of exosomes by tumor cells and alter their encapsulated contents. It also examines the effects of exosomes derived from tumor cells, immune cells, and other cell types under hypoxic conditions on the tumor microenvironment. Additionally, we summarize current research progress on the potential clinical applications of exosomes under hypoxic conditions and propose future research directions in this field.
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Affiliation(s)
- Churan Wang
- Dalian Medical University, Dalian, 116000, People’s Republic of China
| | - Shun Xu
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, 110002, People’s Republic of China
| | - Xiao Yang
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, 110002, People’s Republic of China
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Bermúdez M, Martínez-Barajas MG, Bueno-Urquiza LJ, López-Gutiérrez JA, Villegas-Mercado CE, López-Camarillo C. Role of MicroRNA-204 in Regulating the Hallmarks of Breast Cancer: An Update. Cancers (Basel) 2024; 16:2814. [PMID: 39199587 PMCID: PMC11352763 DOI: 10.3390/cancers16162814] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 08/01/2024] [Accepted: 08/09/2024] [Indexed: 09/01/2024] Open
Abstract
microRNA-204-5p (miR-204) is a small noncoding RNA with diverse regulatory roles in breast cancer (BC) development and progression. miR-204 is implicated in the instauration of fundamental traits acquired during the multistep development of BC, known as the hallmarks of cancer. It may act as a potent tumor suppressor by inhibiting key cellular processes like angiogenesis, vasculogenic mimicry, invasion, migration, and metastasis. It achieves this by targeting multiple master genes involved in these processes, including HIF-1α, β-catenin, VEGFA, TGFBR2, FAK, FOXA1, among others. Additionally, miR-204 modulates signaling pathways like PI3K/AKT and interacts with HOTAIR and DSCAM-AS1 lncRNAs, further influencing tumor progression. Beyond its direct effects on tumor cells, miR-204 shapes the tumor microenvironment by regulating immune cell infiltration, suppressing pro-tumorigenic cytokine production, and potentially influencing immunotherapy response. Moreover, miR-204 plays a crucial role in metabolic reprogramming by directly suppressing metabolic genes within tumor cells, indirectly affecting metabolism through exosome signaling, and remodeling metabolic flux within the tumor microenvironment. This review aims to present an update on the current knowledge regarding the role of miR-204 in the hallmarks of BC. In conclusion, miR-204 is a potential therapeutic target and prognostic marker in BC, emphasizing the need for further research to fully elucidate its complex roles in orchestrating aggressive BC behavior.
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Affiliation(s)
- Mercedes Bermúdez
- Faculty of Dentistry, Autonomous University of Chihuahua, Chihuahua 31000, Mexico;
| | | | - Lesly Jazmín Bueno-Urquiza
- University Center for Health Sciences, University of Guadalajara, Guadalajara 44340, Mexico; (M.G.M.-B.); (L.J.B.-U.)
| | - Jorge Armando López-Gutiérrez
- Faculty of Dentistry, Autonomous University of Sinaloa, Josefa Ortiz de Domínguez s/n y Avenida de las Américas, Culiacan 80013, Mexico;
| | | | - César López-Camarillo
- Genomic Sciences Program, Autonomous University of Mexico City, San Lorenzo 290, Col del Valle, Mexico City 03100, Mexico
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41
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Li H, Hou M, Zhang P, Ren L, Guo Y, Zou L, Cao J, Bai Z. Wedelolactone suppresses breast cancer growth and metastasis via regulating TGF-β1/Smad signaling pathway. J Pharm Pharmacol 2024; 76:1038-1050. [PMID: 38848454 DOI: 10.1093/jpp/rgae065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 06/03/2024] [Indexed: 06/09/2024]
Abstract
OBJECTIVE Breast cancer is a malignant tumor with high invasion and metastasis. TGF-β1-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of breast cancer. Wedelolactone (Wed) is extracted from herbal medicine Ecliptae Herba, which is reported to have antineoplastic activity. Here, we aimed to elucidate the efficacy and mechanism of Wed against breast cancer. METHODS The effects of Wed on migration and invasion of 4T1 were detected. The expression of EMT-related markers was detected by Western blot and qPCR. The 4T1 orthotopic murine breast cancer model was established to evaluate the therapeutic effect of Wed on the growth and metastasis of breast cancer through TGF-β1/Smad pathway. RESULTS Wed inhibited the proliferation, migration and invasion of 4T1. It exhibited concentration-dependent inhibition of p-Smad2/3. Wed also reversed the expression of EMT-markers induced by TGF-β1. In addition, Wed suppressed the growth and metastasis of breast cancer in mice. It also affected p-Smad3 expression as well as EMT-related genes, suggesting that its anti-breast cancer effect may be related to the TGF-β1/Smad pathway. CONCLUSION Wed reverses EMT by regulating TGF-β1/Smad pathway, potentially serving as a therapeutic agent for breast cancer. Wed is expected to be a potential drug to inhibit TGF-β1/Smad pathway-related diseases.
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Affiliation(s)
- Hui Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
- Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
- China Military Institute of Chinese Materia, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
| | - Manting Hou
- Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
- China Military Institute of Chinese Materia, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
| | - Ping Zhang
- Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing 100853, China
| | - Lutong Ren
- Department of Pharmacy, Inner Mongolia People's Hospital, Hohhot 010010, China
| | - Yuanyuan Guo
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
- Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
- China Military Institute of Chinese Materia, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
| | - Liang Zou
- School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China
| | - Junling Cao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Zhaofang Bai
- Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
- China Military Institute of Chinese Materia, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
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42
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Nathanson SD, Dieterich LC, Zhang XHF, Chitale DA, Pusztai L, Reynaud E, Wu YH, Ríos-Hoyo A. Associations amongst genes, molecules, cells, and organs in breast cancer metastasis. Clin Exp Metastasis 2024; 41:417-437. [PMID: 37688650 DOI: 10.1007/s10585-023-10230-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 08/18/2023] [Indexed: 09/11/2023]
Abstract
This paper is a cross fertilization of ideas about the importance of molecular aspects of breast cancer metastasis by basic scientists, a pathologist, and clinical oncologists at the Henry Ford Health symposium. We address four major topics: (i) the complex roles of lymphatic endothelial cells and the molecules that stimulate them to enhance lymph node and systemic metastasis and influence the anti-tumor immunity that might inhibit metastasis; (ii) the interaction of molecules and cells when breast cancer spreads to bone, and how bone metastases may themselves spread to internal viscera; (iii) how molecular expression and morphologic subtypes of breast cancer assist clinicians in determining which patients to treat with more or less aggressive therapies; (iv) how the outcomes of patients with oligometastases in breast cancer are different from those with multiple metastases and how that could justify the aggressive treatment of these patients with the hope of cure.
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Affiliation(s)
- S David Nathanson
- Department of Surgery, Henry Ford Health, 2799 W. Grand Blvd, Detroit, MI, 48202, USA.
- Cancer Center, Henry Ford Health, Detroit, MI, USA.
| | - Lothar C Dieterich
- European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany
| | - Xiang H-F Zhang
- Lester and Sue Smith Breast Center, Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
| | | | - Lajos Pusztai
- Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA
| | - Emma Reynaud
- European Center for Angioscience (ECAS), Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany
| | - Yi-Hsuan Wu
- Lester and Sue Smith Breast Center, Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA
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Nosaka T, Murata Y, Akazawa Y, Takahashi K, Naito T, Matsuda H, Ohtani M, Nakamoto Y. Changes of circulating tumor cells expressing CD90 and EpCAM in early-phase of atezolizumab and bevacizumab for hepatocellular carcinoma. Heliyon 2024; 10:e34441. [PMID: 39108869 PMCID: PMC11301359 DOI: 10.1016/j.heliyon.2024.e34441] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 07/08/2024] [Accepted: 07/09/2024] [Indexed: 01/03/2025] Open
Abstract
Circulating tumor cells (CTCs) are noninvasive biomarkers that can indicate the therapeutic response and prognosis. The study aimed to investigate the cellular characteristics of CTCs focusing on monitoring during atezolizumab and bevacizumab (Atezo-Bev) therapy in patients with hepatocellular carcinoma (HCC). Peripheral blood samples were collected from 10 healthy controls and 40 patients with HCC. CTCs enriched using RosetteSep™ Human CD45 depletion cocktail were analyzed by multiparametric flow cytometry. CTC isolation was based on PanCK(+)CD45(-) cells, and CTCs exhibiting markers CD90, CD133, EpCAM, or vimentin. The total number of CTCs and the number of CTCs expressing CD90, CD133, EpCAM, and vimentin were correlated with the BCLC stage of HCC. The change in total CTC count accurately reflected the initial response to Atezo-Bev therapy. The numbers and mean fluorescence intensity of the CTC subsets expressing CD90 and EpCAM molecules decreased in patients with partial response/stable disease, and increased in patients with progressive disease and were markedly correlated with overall survival. CD90(+) and EpCAM(+) CTCs may be candidate biomarkers for the early prediction of the treatment response and the overall survival of patients with HCC receiving Atezo-Bev therapy.
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Affiliation(s)
- Takuto Nosaka
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yosuke Murata
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yu Akazawa
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Kazuto Takahashi
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Tatsushi Naito
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Hidetaka Matsuda
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masahiro Ohtani
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yasunari Nakamoto
- Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
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Peng Z, Yi Y, Nie Y, Wang T, Tang J, Hong S, Liu Y, Huang W, Sun S, Tan H, Wu M. Softening the tumor matrix through cholesterol depletion breaks the physical barrier for enhanced antitumor therapy. J Control Release 2024; 371:29-42. [PMID: 38763389 DOI: 10.1016/j.jconrel.2024.05.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 05/15/2024] [Accepted: 05/16/2024] [Indexed: 05/21/2024]
Abstract
The tumor develops defense tactics, including conversing the mechanical characteristics of tumor cells and their surrounding environment. A recent study reported that cholesterol depletion stiffens tumor cells, which could enhance adaptive T-cell immunotherapy. However, it remains unclear whether reducing the cholesterol in tumor cells contributes to re-educating the stiff tumor matrix, which serves as a physical barrier against drug penetration. Herein, we found that depleting cholesterol from tumor cells can demolish the intratumor physical barrier by disrupting the mechanical signal transduction between tumor cells and the extracellular matrix through the destruction of lipid rafts. This disruption allows nanoparticles (H/S@hNP) to penetrate deeply, resulting in improved photodynamic treatment. Our research also indicates that cholesterol depletion can inhibit the epithelial-mesenchymal transition and repolarize tumor-associated macrophages from M2 to M1, demonstrating the essential role of cholesterol in tumor progression. Overall, this study reveals that a cholesterol-depleted, softened tumor matrix reduces the difficulty of drug penetration, leading to enhanced antitumor therapeutics.
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Affiliation(s)
- Zhangwen Peng
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
| | - Yunfei Yi
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
| | - Yichu Nie
- Department of Translational Medicine Research Institute, First People's Hospital of Foshan, Foshan 528000, China
| | - Tianqi Wang
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
| | - Jia Tang
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
| | - Sheng Hong
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
| | - Yuanqi Liu
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
| | - Wenxin Huang
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
| | - Shengjie Sun
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China
| | - Hui Tan
- Center for Child Care and Mental Health (CCCMH), Shenzhen Children's Hospital, Shenzhen 518038, China.
| | - Meiying Wu
- School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, China.
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Lu B, Liao SM, Liang SJ, Li JX, Liu XH, Huang RB, Zhou GP. NMR Studies of the Interactions between Sialyllactoses and the Polysialytransferase Domain for Polysialylation Inhibition. Curr Issues Mol Biol 2024; 46:5682-5700. [PMID: 38921011 PMCID: PMC11201969 DOI: 10.3390/cimb46060340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 04/30/2024] [Accepted: 05/26/2024] [Indexed: 06/27/2024] Open
Abstract
It is known that sialyllactose (SL) in mammalians is a major source of sialic acid (Sia), which can further form cytidine monophosphate sialic acid (CMP-Sia), and the final product is polysialic acid (polySia) using polysialyltransferases (polySTs) on the neural cell adhesion molecule (NCAM). This process is called NCAM polysialylation. The overexpression of polysialylation is strongly related to cancer cell migration, invasion, and metastasis. In order to inhibit the overexpression of polysialylation, in this study, SL was selected as an inhibitor to test whether polysialylation could be inhibited. Our results suggest that the interactions between the polysialyltransferase domain (PSTD) in polyST and CMP-Siaand the PSTD and polySia could be inhibited when the 3'-sialyllactose (3'-SL) or 6'-sialyllactose (6'-SL) concentration is about 0.5 mM or 6'-SL and 3 mM, respectively. The results also show that SLs (particularly for 3'-SL) are the ideal inhibitors compared with another two inhibitors, low-molecular-weight heparin (LMWH) and cytidine monophosphate (CMP), because 3'-SL can not only be used to inhibit NCAM polysialylation, but is also one of the best supplements for infant formula and the gut health system.
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Affiliation(s)
- Bo Lu
- National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning 530007, China; (B.L.); (S.-M.L.); (S.-J.L.); (J.-X.L.)
| | - Si-Ming Liao
- National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning 530007, China; (B.L.); (S.-M.L.); (S.-J.L.); (J.-X.L.)
| | - Shi-Jie Liang
- National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning 530007, China; (B.L.); (S.-M.L.); (S.-J.L.); (J.-X.L.)
| | - Jian-Xiu Li
- National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning 530007, China; (B.L.); (S.-M.L.); (S.-J.L.); (J.-X.L.)
| | - Xue-Hui Liu
- Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
| | - Ri-Bo Huang
- National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning 530007, China; (B.L.); (S.-M.L.); (S.-J.L.); (J.-X.L.)
- Life Science and Technology College, Guangxi University, Nanning 530004, China
- Rocky Mount Life Science Institute, Rocky Mount, NC 27804, USA
| | - Guo-Ping Zhou
- National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, 98 Daling Road, Nanning 530007, China; (B.L.); (S.-M.L.); (S.-J.L.); (J.-X.L.)
- Rocky Mount Life Science Institute, Rocky Mount, NC 27804, USA
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46
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Thakur C, Qiu Y, Pawar A, Chen F. Epigenetic regulation of breast cancer metastasis. Cancer Metastasis Rev 2024; 43:597-619. [PMID: 37857941 DOI: 10.1007/s10555-023-10146-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 10/02/2023] [Indexed: 10/21/2023]
Abstract
Breast cancer is the most frequently diagnosed malignancy and the second leading cause of cancer-related mortality among women worldwide. Recurrent metastasis is associated with poor patient outcomes and poses a significant challenge in breast cancer therapies. Cancer cells adapting to a new tissue microenvironment is the key event in distant metastasis development, where the disseminating tumor cells are likely to acquire genetic and epigenetic alterations during the process of metastatic colonization. Despite several decades of research in this field, the exact mechanisms governing metastasis are not fully understood. However, emerging body of evidence indicates that in addition to genetic changes, epigenetic reprogramming of cancer cells and the metastatic niche are paramount toward successful metastasis. Here, we review and discuss the latest knowledge about the salient attributes of metastasis and epigenetic regulation in breast cancer and crucial research domains that need further investigation.
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Affiliation(s)
- Chitra Thakur
- Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY, 11794, USA.
| | - Yiran Qiu
- Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY, 11794, USA
| | - Aashna Pawar
- Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY, 11794, USA
| | - Fei Chen
- Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY, 11794, USA.
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47
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Haake SM, Rios BL, Pozzi A, Zent R. Integrating integrins with the hallmarks of cancer. Matrix Biol 2024; 130:20-35. [PMID: 38677444 DOI: 10.1016/j.matbio.2024.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 04/02/2024] [Accepted: 04/23/2024] [Indexed: 04/29/2024]
Abstract
Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular matrix provides essential physical scaffolding and biochemical and biophysical cues required for tissue morphogenesis, differentiation, function, and homeostasis. Epithelial cell adhesion to the extracellular matrix (i.e., basement membrane) plays a critical role in organizing epithelial tissues, separating the epithelial cells from the stroma. Epithelial cell detachment from the basement membrane classically results in death, though detachment or invasion through the basement membrane represents a critical step in carcinogenesis. Epithelial cells bind to the extracellular matrix via specialized matrix receptors, including integrins. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. The role of integrins in the development, growth, and dissemination of multiple types of carcinomas has been investigated by numerous methodologies, which has led to great complexity. To organize this vast array of information, we have utilized the "Hallmarks of Cancer" from Hanahan and Weinberg as a convenient framework to discuss the role of integrins in the pathogenesis of cancers. This review explores this biology and how its complexity has impacted the development of integrin-targeted anti-cancer therapeutics.
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Affiliation(s)
- Scott M Haake
- Division of Hematology, Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Veterans Affairs, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Cancer Biology Program, Vanderbilt University, Nashville, TN, USA.
| | - Brenda L Rios
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Cancer Biology Program, Vanderbilt University, Nashville, TN, USA
| | - Ambra Pozzi
- Department of Veterans Affairs, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Roy Zent
- Department of Veterans Affairs, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; Cancer Biology Program, Vanderbilt University, Nashville, TN, USA; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
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48
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Kalashgrani MY, Mousavi SM, Akmal MH, Gholami A, Omidifar N, Chiang WH, Lai CW, Ripaj Uddin M, Althomali RH, Rahman MM. Biosensors for metastatic cancer cell detection. Clin Chim Acta 2024; 559:119685. [PMID: 38663472 DOI: 10.1016/j.cca.2024.119685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 04/21/2024] [Accepted: 04/22/2024] [Indexed: 05/04/2024]
Abstract
Early detection and effective cancer treatment are critical to improving metastatic cancer cell diagnosis and management today. In particular, accurate qualitative diagnosis of metastatic cancer cell represents an important step in the diagnosis of cancer. Today, biosensors have been widely developed due to the daily need to measure different chemical and biological species. Biosensors are utilized to quantify chemical and biological phenomena by generating signals that are directly proportional to the quantity of the analyte present in the reaction. Biosensors are widely used in disease control, drug delivery, infection detection, detection of pathogenic microorganisms, and markers that indicate a specific disease in the body. These devices have been especially popular in the field of metastatic cancer cell diagnosis and treatment due to their portability, high sensitivity, high specificity, ease of use and short response time. This article examines biosensors for metastatic cancer cells. It also studies metastatic cancer cells and the mechanism of metastasis. Finally, the function of biosensors and biomarkers in metastatic cancer cells is investigated.
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Affiliation(s)
| | - Seyyed Mojtaba Mousavi
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taiwan
| | - Muhammad Hussnain Akmal
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taiwan
| | - Ahmad Gholami
- Biotechnology Research Center, Shiraz University of Medical Science, Shiraz, Iran
| | - Navid Omidifar
- Department of Pathology, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran
| | - Wei-Hung Chiang
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taiwan.
| | - Chin Wei Lai
- Nanotechnology and Catalysis Research Centre (NANOCAT), Level 3, Block A, Institute for Advanced Studies (IAS), Universiti Malaya (UM), 50603 Kuala Lumpur, Malaysia
| | - Md Ripaj Uddin
- Institute of National Analytical Research and Service (INARS), Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhanmondi, Dhaka, Bangladesh
| | - Raed H Althomali
- Department of Chemistry, College of Art and Science, Prince Sattam bin Abdulaziz University, Wadi Al-Dawasir 11991, Al Kharj, Saudi Arabia
| | - Mohammed M Rahman
- Center of Excellence for Advanced Materials Research (CEAMR) & Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.
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49
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Deng S, Wu Y, Huang S, Yang X. Novel insights into the roles of migrasome in cancer. Discov Oncol 2024; 15:166. [PMID: 38748047 PMCID: PMC11096295 DOI: 10.1007/s12672-024-00942-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 03/18/2024] [Indexed: 05/18/2024] Open
Abstract
Cell migration, a hallmark of cancer malignancy, plays a critical role in cancers. Improperly initiated or misdirected cell migration can lead to invasive metastatic cancer. Migrasomes are newly discovered vesicular cellular organelles produced by migrating cells and depending on cell migration. Four marker proteins [NDST1 (bifunctionalheparan sulfate N-deacetylase/N-sulfotransferase 1), EOGT (Epidermal growth factor domains pecific O-linked N-acetylglucosaminetransferase), CPQ (carboxypeptidase Q), and PIGK (phosphatidylinositol glycan anchor biosynthesis, class K)] of migrasomes were successfully identified. There are three marker proteins (NDST1, PIGK, and EOGT) of migrasome expressed in cancer. In this review, we will discuss the process of migrasome discovery, the formation of migrasome, the possible functions of migrasome, and the differences between migrasomes and exosomes, especially, the biological functions of migrasome marker proteins in cancer, and discuss some possible roles of migrasomes in cancer. We speculate that migrasomes and migracytosis can play key roles in regulating the development of cancer.
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Affiliation(s)
- Sijun Deng
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang , 421001, Hunan, People's Republic of China
| | - Yiwen Wu
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang , 421001, Hunan, People's Republic of China
| | - Sheng Huang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang , 421001, Hunan, People's Republic of China
| | - Xiaoyan Yang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang , 421001, Hunan, People's Republic of China.
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50
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Ashrafizadeh M, Dai J, Torabian P, Nabavi N, Aref AR, Aljabali AAA, Tambuwala M, Zhu M. Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance. Cell Mol Life Sci 2024; 81:214. [PMID: 38733529 PMCID: PMC11088560 DOI: 10.1007/s00018-024-05236-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 03/05/2024] [Accepted: 04/03/2024] [Indexed: 05/13/2024]
Abstract
The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of Radiation Oncology, Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong 250000, China
- Department of General Surgery and Integrated Chinese and Western Medicine, Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, 518060, China
- Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Jingyuan Dai
- School of computer science and information systems, Northwest Missouri State University, Maryville, MO, 64468, USA.
| | - Pedram Torabian
- Cumming School of Medicine, Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, AB, T2N 4Z6, Canada
- Department of Medical Sciences, University of Calgary, Calgary, AB, T2N 4Z6, Canada
| | - Noushin Nabavi
- Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, V6H3Z6, Canada
| | - Amir Reza Aref
- Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
- Department of Translational Sciences, Xsphera Biosciences Inc. Boston, Boston, MA, USA
| | - Alaa A A Aljabali
- Faculty of Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid, Jordan
| | - Murtaza Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln, LN6 7TS, UK.
- College of Pharmacy, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates.
| | - Minglin Zhu
- Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
- Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan, Hubei, 430071, China.
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