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Yadav SS, Srinivasan K, Sharma SS, Datusalia AK. Decoding the Nectin Interactome: Implications for Brain Development, Plasticity, and Neurological Disorders. ACS Chem Neurosci 2025; 16:1000-1020. [PMID: 40025835 DOI: 10.1021/acschemneuro.5c00069] [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] [Indexed: 03/04/2025] Open
Abstract
The nectin family of cell adhesion molecules (CAMs) comprising nectins and nectin-like molecules has emerged as a key regulator of various pivotal neural processes, including neuronal development, migration, synapse formation, and plasticity. Nectins engage in homophilic and heterophilic interactions to mediate cell-cell adhesion, contributing to the establishment and maintenance of neural circuits. Their extracellular domains facilitate trans-synaptic interactions, while intracellular domains participate in signaling cascades influencing cytoskeletal dynamics and synaptic function. The exhibition of distinct localization patterns in neurons, astrocytes, and the blood-brain barrier underscores their diverse roles in the brain. The dysregulation of nectins has been implicated in several neurological disorders, such as neurodevelopmental disorders, depression, schizophrenia, and Alzheimer's disease. This review examines the structural and functional characteristics of nectins and their distribution and molecular mechanisms governing neural connectivity and cognition. It further discusses experimental studies unraveling nectin-mediated pathophysiology and potential therapeutic interventions targeting nectin-related pathways. Collectively, this comprehensive analysis highlights the significance of nectins in brain development, function, and disorders, paving the way for future research directions and clinical implications.
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Affiliation(s)
- Shreyash Santosh Yadav
- Molecular NeuroTherapeutics Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, Uttar Pradesh 226002, India
| | - Krishnamoorthy Srinivasan
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India
| | - Shyam Sunder Sharma
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India
| | - Ashok Kumar Datusalia
- Molecular NeuroTherapeutics Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli, Uttar Pradesh 226002, India
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Liu Y, Lyu D, Yao Y, Cui J, Liu J, Bai Z, Zhao Z, Li Y, Lu B, Dong K, Pan X. The comprehensive potential of AQP1 as a tumor biomarker: evidence from kidney neoplasm cohorts, cell experiments and pan-cancer analysis. Hum Genomics 2025; 19:15. [PMID: 39988693 PMCID: PMC11849320 DOI: 10.1186/s40246-025-00726-9] [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: 12/22/2024] [Accepted: 02/12/2025] [Indexed: 02/25/2025] Open
Abstract
Aquaporin1 (AQP1) facilitates water transport. Its ability to be a biomarker at the pan-cancer level remains uninvestigated. We performed immunohistochemical staining on tissues from 370 individuals with kidney neoplasms to measure AQP1 expression. We utilized Kaplan-Meier survival analysis, Chi-square tests, and multivariate Cox regression analyses to assess the prognostic relevance of AQP1 expression. In the pan-cancer context, we explored AQP1's competing endogenous RNAs network, protein-protein interactions, genomic changes, gene set enrichment analysis (GSEA), the correlation of AQP1 expression with survival outcomes, drug sensitivity, drug molecular docking, tumor purity and immunity. AQP1 shRNA expressing 786-O cells were established. Cell proliferation was assessed by Cell Counting Kit-8 and colony formation. Transwell migration, invasion, and cell scratch assays were conducted. In our study, AQP1 expression was an independent protective factor for OS and PFS in renal cancer patients. AQP1 expression significantly correlated with survival outcomes in renal cancers, LGG, SARC, HNSC and UVM. PI-103 sensitivity was related to AQP1 expression and had potential binding cite with AQP1 protein. Knockdown of AQP1 reduced cell proliferation, migration and invasion. Our study uncovered AQP1 as a biomarker for favorable survival outcomes in renal cancers. Furthermore, the bioinformatic analysis promoted its implication in pan-cancer scope.
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Affiliation(s)
- Yifan Liu
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- BGI research, BGI-Hangzhou, Hangzhou, 310012, China
| | - Donghao Lyu
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yuntao Yao
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- BGI research, BGI-Hangzhou, Hangzhou, 310012, China
| | - Jinming Cui
- Ulink College of Shanghai, Shanghai, 201615, China
| | - Jiangui Liu
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Zikuan Bai
- Shanghai YK Pao School, Shanghai, 201620, China
| | - Zihui Zhao
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yuanan Li
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Bingnan Lu
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
| | - Keqin Dong
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
- Department of urology, Chinese PLA general hospital of central theater command, Wuhan, 430061, China.
| | - Xiuwu Pan
- Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
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Zhang S, Huang J, Jiang Z, Tong H, Ma X, Liu Y. Tumor microbiome: roles in tumor initiation, progression, and therapy. MOLECULAR BIOMEDICINE 2025; 6:9. [PMID: 39921821 PMCID: PMC11807048 DOI: 10.1186/s43556-025-00248-9] [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: 08/02/2024] [Revised: 01/06/2025] [Accepted: 01/21/2025] [Indexed: 02/10/2025] Open
Abstract
Over the past few years, the tumor microbiome is increasingly recognized for its multifaceted involvement in cancer initiation, progression, and metastasis. With the application of 16S ribosomal ribonucleic acid (16S rRNA) sequencing, the intratumoral microbiome, also referred to as tumor-intrinsic or tumor-resident microbiome, has also been found to play a significant role in the tumor microenvironment (TME). Understanding their complex functions is critical for identifying new therapeutic avenues and improving treatment outcomes. This review first summarizes the origins and composition of these microbial communities, emphasizing their adapted diversity across a diverse range of tumor types and stages. Moreover, we outline the general mechanisms by which specific microbes induce tumor initiation, including the activation of carcinogenic pathways, deoxyribonucleic acid (DNA) damage, epigenetic modifications, and chronic inflammation. We further propose the tumor microbiome may evade immunity and promote angiogenesis to support tumor progression, while uncovering specific microbial influences on each step of the metastatic cascade, such as invasion, circulation, and seeding in secondary sites. Additionally, tumor microbiome is closely associated with drug resistance and influences therapeutic efficacy by modulating immune responses, drug metabolism, and apoptotic pathways. Furthermore, we explore innovative microbe-based therapeutic strategies, such as engineered bacteria, oncolytic virotherapy, and other modalities aimed at enhancing immunotherapeutic efficacy, paving the way for microbiome-centered cancer treatment frameworks.
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Affiliation(s)
- Shengxin Zhang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Jing Huang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan Province, China
| | - Zedong Jiang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Huan Tong
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Xuelei Ma
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - Yang Liu
- Day Surgery Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
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Li M, Chen L, Wang M, Huang X, Ke Q, Hu C. Curcumin alleviates the aggressiveness of breast cancer through inhibiting cell adhesion mediated by TEAD4-fibronectin axis. Biochem Pharmacol 2025; 232:116690. [PMID: 39617209 DOI: 10.1016/j.bcp.2024.116690] [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: 08/17/2024] [Revised: 10/14/2024] [Accepted: 11/28/2024] [Indexed: 12/15/2024]
Abstract
Breast cancer (BC) ranks first among women in the world and metastasis is the main reason of cancer death. TEA domain transcription factor 4 (TEAD4) plays an important role in TEAD family members in the Hippo signaling pathway, and its pro-cancer effect is gradually being discovered, but little is known about the mechanism of TEAD4 regulating tumor adhesion and metastasis. Curcumin is an active polyphenol compound with anti-inflammatory and anti-tumor properties. However, its effects and the underlying mechanisms on BC metastasis remain unknown. Here, we show that curcumin reduced the abilities of migration and invasion of BC cells as well as lung metastasis of BC in nude mice by TEAD4 induced. TEAD4 could regulate the transcription level of adhesion molecule Fibronectin (FN1), which is an important component of extracellular matrix participating in tumor cell adhesion and migration processes, and the binding of TEAD4 to the FN1 promoter was suppressed by curcumin. Furthermore, the metastatic mobility was significantly reduced in FN1 knockout BC cells, and FN1 knockout can reverse metastatic potential of TEAD4 overexpressed cells. Our work demonstrates that TEAD4 can promote cell adhesion and migration by binding with FN1 promoter and suggests that TEAD4-FN1 axis in tumor microenvironment is expected to become a potential target for alleviating metastasis of BC of curcumin. Abbreviations: Breast cancer (BC); Bicinchoninic acid (BCA); Bovine Serum Albumin (BSA); Curcumin at 20 μM (Cur20) and 30 μM (Cur30); Dimethyl -sulfoxide (DMSO); Dulbecco's Modified Eagle's Medium (DMEM); Extracellular Matrix (ECM); Fetal bovine serum (FBS); Fibronectin (FN1); Immunohistochemical (IHC); Minimum Essential Medium (MEM); The negative control with infected blank lentivirus (NC); Phenylmethanesulfonyl fluoride (PMSF); Polyvinylidene difluoride (PVDF); Real-time quantitative reverse transcription (RT-qPCR); single guide RNA (sgRNA); short hairpin RNA (shRNA); Human TEAD4 shRNA (shTEAD4); Transcriptional coactivator with PDZ-binding motif (TAZ); TEA domain transcription factor 4 (TEAD4); TEAD4 overexpressed (TEAD4-OE); Vascular endothelial growth factor (VEGF); Yes-associated protein (YAP).
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Affiliation(s)
- Mengjie Li
- School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China
| | - Lihua Chen
- School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China
| | - Miao Wang
- School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China
| | - Xia Huang
- School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China
| | - Qiaodan Ke
- School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China
| | - Chenxia Hu
- School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
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Xu J, Koch J, Schmidt C, Nientiedt M, Neuberger M, Erben P, Michel MS, Rodríguez-Paredes M, Lyko F. Loss of YTHDC1 m 6A reading function promotes invasiveness in urothelial carcinoma of the bladder. Exp Mol Med 2025; 57:118-130. [PMID: 39741187 PMCID: PMC11799412 DOI: 10.1038/s12276-024-01377-x] [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: 05/24/2024] [Revised: 09/18/2024] [Accepted: 10/06/2024] [Indexed: 01/02/2025] Open
Abstract
Bladder cancer poses significant clinical challenges due to its high metastatic potential and poor prognosis, especially when it progresses to muscle-invasive stages. Here, we show that the m6A reader YTHDC1 is downregulated in muscle-invasive bladder cancer and is negatively correlated with the expression of epithelial‒mesenchymal transition genes. The functional inhibition or depletion of YTHDC1 increased the migration and invasion of urothelial cells. Integrative analysis of multimodal sequencing datasets provided detailed insights into the molecular mechanisms mediating YTHDC1-dependent phenotypes and identified SMAD6 as a key transcript involved in the invasiveness of urothelial carcinoma of the bladder. Notably, SMAD6 mRNA colocalized less with YTHDC1 in tumoral tissues than in paratumoral tissues, indicating disrupted binding during cancer progression. Our findings establish YTHDC1-dependent m6A reading as a critical epitranscriptomic mechanism regulating bladder cancer invasiveness and provide a paradigm for the epitranscriptomic deregulation of cancer-associated networks.
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Affiliation(s)
- Jinyun Xu
- Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany
| | - Jonas Koch
- Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany
| | - Claudia Schmidt
- Core Facility Unit Light Microscopy, German Cancer Research Center, 69120, Heidelberg, Germany
| | - Malin Nientiedt
- Department of Urology and Urosurgery, Medical Faculty Mannheim, University of Heidelberg, 68167, Mannheim, Germany
| | - Manuel Neuberger
- Department of Urology and Urosurgery, Medical Faculty Mannheim, University of Heidelberg, 68167, Mannheim, Germany
| | - Philipp Erben
- Department of Urology and Urosurgery, Medical Faculty Mannheim, University of Heidelberg, 68167, Mannheim, Germany
| | - Maurice Stephan Michel
- Department of Urology and Urosurgery, Medical Faculty Mannheim, University of Heidelberg, 68167, Mannheim, Germany
| | - Manuel Rodríguez-Paredes
- Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany
| | - Frank Lyko
- Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, 69120, Heidelberg, Germany.
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Shmelev ME, Pilnik AA, Shved NA, Penkova AO, Gulaia VS, Kumeiko VV. IDH1 R132H and TP53 R248Q Mutations Modulate Glioma Cell Migration and Adhesion on Different ECM Components. Int J Mol Sci 2024; 25:12178. [PMID: 39596246 PMCID: PMC11594609 DOI: 10.3390/ijms252212178] [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: 10/22/2024] [Revised: 11/09/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
Mutations in IDH1 and TP53 have a significant impact on glioma prognosis and progression; however, their roles in tumor cell invasion in terms of interactions with particular components of the extracellular matrix (ECM) are still unclear. Using gene editing protocol based on CRISPR-Cas 9 with cytidine deaminase, we introduced point mutations into U87MG glioblastoma cells to establish modified cell lines with heterozygous IDH1 R132H, homozygous TP53 R248Q and heterozygous IDH1 R132H, homozygous TP53 R248Q genotypes. A comparative study of cell migration on major ECM components was carried out by high-content microscopy. IDH1 R132H mutation introduced to U87MG glioblastoma cells was shown to decrease the migration speed on Matrigel and collagen IV substrates compared to the wild-type. This data were supported by cell adhesion quantification via the lateral shift assay performed by atomic force microscopy (AFM). TP53 R248Q mutation increased cell adhesion to various substrates and significantly promoted cell migration on hyaluronic acid and chondroitin sulfate but did not change the migration rates on laminin and collagens IV and I. A double-mutant genotype produced by consequently introducing IDH1 R132H and TP53 R248Q to parental glioblastoma cells was characterized by the highest migration among all the cell lines, with particularly faster motility on chondroitin sulfate. These findings underscore the complex interactions between glioma cells, with the most important driver mutations and specific ECM components regulating cancer cell migration, offering valuable insights for potential therapeutic targets in glioma treatment.
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Affiliation(s)
- Mikhail E. Shmelev
- School of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, Russia
- A.V. Zhirmunsky National Scientific Center of Marine Biology Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690041, Russia
| | - Andrei A. Pilnik
- School of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, Russia
| | - Nikita A. Shved
- School of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, Russia
- A.V. Zhirmunsky National Scientific Center of Marine Biology Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690041, Russia
| | - Alina O. Penkova
- School of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, Russia
| | - Valeriia S. Gulaia
- School of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, Russia
| | - Vadim V. Kumeiko
- School of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, Russia
- A.V. Zhirmunsky National Scientific Center of Marine Biology Far Eastern Branch of Russian Academy of Sciences, Vladivostok 690041, Russia
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7
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Liao M, Zheng W, Wang Y, Li M, Sun X, Liu N, Yao J, Dong F, Wang Q, Ma Y, Mou J. LINC00887 promotes GCN5-dependent H3K27cr level and CRC metastasis via recruitment of YEATS2 and enhancing ETS1 expression. Cell Death Dis 2024; 15:711. [PMID: 39349460 PMCID: PMC11443008 DOI: 10.1038/s41419-024-07091-w] [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: 04/02/2024] [Revised: 09/15/2024] [Accepted: 09/18/2024] [Indexed: 10/02/2024]
Abstract
Recent observations have revealed upregulation of H3K27cr in colorectal cancer (CRC) tissues; however, the underlying cause remains elusive. This study aimed to investigate the mechanism of H3K27cr upregulation and its roles in CRC metastasis. Clinically, our findings showed that H3K27cr served as a highly accurate diagnostic marker to distinguish CRC tissues from healthy controls. Elevated levels of LINC00887 and H3K27cr were associated with a poorer prognosis in CRC patients. Functionally, LINC00887 and H3K27cr facilitated the migration and invasion of CRC cells. Mechanistically, LINC00887 interacted with SIRT3 protein. Overexpressed of LINC00887 obstructed the enrichment of SIRT3 within GCN5 promoter, thereby elevating H3K27ac but not H3K27cr level within this region, subsequently activating GCN5 expression. This activation increased the global level of H3K27cr, promoting the enrichment of GCN5, H3K27cr, and YEATS2 within ETS1 promoter, activating ETS1 transcription and ultimately promoting the metastasis of CRC. The in vivo study demonstrated that inhibition of LINC00887 suppressed CRC metastasis, but this inhibitory effect was nullified when mice were treated with NaCr. In conclusion, our results confirmed the diagnostic biomarker potential of H3K27cr in individuals with CRC, and proposed a functional model to elucidate the involvement of LINC00887 in promoting CRC metastasis by elevating H3K27cr level.
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Affiliation(s)
- Meijian Liao
- Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, PR China
| | - Wendan Zheng
- Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, PR China
| | - Yifan Wang
- Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, PR China
| | - Mengting Li
- Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, PR China
| | - Xiaolin Sun
- Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, PR China
| | - Nan Liu
- Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, the First Hospital of Jilin University, Changchun, 130061, PR China
- Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, the First Hospital of Jilin University, Changchun, 130061, PR China
| | - Jia Yao
- Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, PR China
| | - Fuxing Dong
- Public Experimental Research Center, Xuzhou Medical University, Xuzhou, 221004, PR China
| | - Qingling Wang
- Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, PR China
| | - Yu Ma
- Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, PR China.
| | - Jie Mou
- School of Pharmacy, Xuzhou Medical University, Xuzhou, 221004, PR China.
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Krawczyk-Wołoszyn K, Roczkowski D, Reich A, Żychowska M. Applying the Atomic Force Microscopy Technique in Medical Sciences-A Narrative Review. Biomedicines 2024; 12:2012. [PMID: 39335524 PMCID: PMC11429229 DOI: 10.3390/biomedicines12092012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/25/2024] [Accepted: 08/29/2024] [Indexed: 09/30/2024] Open
Abstract
Penetrating deep into the cells of the human body in real time has become increasingly possible with the implementation of modern technologies in medicine. Atomic force microscopy (AFM) enables the effective live imaging of cellular and molecular structures of biological samples (such as cells surfaces, components of biological membranes, cell nuclei, actin networks, proteins, and DNA) and provides three-dimensional surface visualization (in X-, Y-, and Z-planes). Furthermore, the AFM technique enables the study of the mechanical, electrical, and magnetic properties of cells and cell organelles and the measurements of interaction forces between biomolecules. The technique has found wide application in cancer research. With the use of AFM, it is not only possible to differentiate between healthy and cancerous cells, but also to distinguish between the stages of cancerous conditions. For many years, AFM has been an important tool for the study of neurodegenerative diseases associated with the deposition of peptide amyloid plaques. In recent years, a significant amount of research has been conducted on the application of AFM in the evaluation of connective tissue cell mechanics. This review aims to provide the spectrum of the most important applications of the AFM technique in medicine to date.
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Affiliation(s)
- Karolina Krawczyk-Wołoszyn
- Doctoral School, University of Rzeszow, 35-959 Rzeszów, Poland;
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszów, Poland;
| | - Damian Roczkowski
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszów, Poland;
| | - Adam Reich
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszów, Poland;
| | - Magdalena Żychowska
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-959 Rzeszów, Poland;
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9
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Clark MJ, Moser HJ, Anand RK. Dielectrophoretic capture and electrochemical enzyme-linked immunosorbent assay of single melanoma cells at an array of interlocked spiral bipolar electrodes. ChemElectroChem 2024; 11:e202400182. [PMID: 39483376 PMCID: PMC11526340 DOI: 10.1002/celc.202400182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Indexed: 11/03/2024]
Abstract
Analysis of single cancer cells is critical to obtain accurate patient diagnosis and prognosis. In this work, we report the selective dielectrophoretic capture and electrochemical analysis of single melanoma cells at an array of interlocked spiral bipolar electrodes (iBPEs). Following dielectrophoretic capture, individual melanoma cells are hydrodynamically transferred into picoliter-scale chambers for subsequent analysis. The interlocked spiral end of the iBPE (the sensing pole) is utilized to read out an electrochemical enzyme-linked immunosorbent assay (eELISA), which quantifies the expression of a cell surface antigen, melanoma cell adhesion marker (MCAM). The opposite pole of each BPE is located in a fluidically isolated compartment containing reagents for electrogenerated chemiluminescence (ECL), such that luminescence reports iBPE current. In a preliminary device design, the ECL intensity was insufficient to detect MCAM expression on single cells. To achieve single-cell analysis, we decreased the gap size between the interlocked spirals tenfold (5.0 μm to 0.5 μm), thereby creating a more sensitive biosensor by enhanced redox cycling of the product of eELISA. This work is significant because it allows for the selective isolation and sensitive analysis of individual melanoma cells in a device amenable to point-of-care (POC) application by combining dielectrophoresis (DEP) with interdigitated bipolar electrodes (IDBPEs).
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Affiliation(s)
- Morgan J Clark
- Department of Chemistry, Iowa State University, 1605 Gilman Hall, 2415 Osborn Drive, Ames, IA 50011-1021
| | - Hanna J Moser
- Department of Chemistry, Iowa State University, 1605 Gilman Hall, 2415 Osborn Drive, Ames, IA 50011-1021
| | - Robbyn K Anand
- Department of Chemistry, Iowa State University, 1605 Gilman Hall, 2415 Osborn Drive, Ames, IA 50011-1021
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10
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Song N, Wang Z, Shi P, Cui K, Fan Y, Zeng L, Di W, Li J, Su W, Wang H. Comprehensive analysis of signaling lymphocyte activation molecule family as a prognostic biomarker and correlation with immune infiltration in clear cell renal cell carcinoma. Oncol Lett 2024; 28:354. [PMID: 38881710 PMCID: PMC11176890 DOI: 10.3892/ol.2024.14487] [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: 11/01/2023] [Accepted: 04/17/2024] [Indexed: 06/18/2024] Open
Abstract
Clear cell renal cell carcinoma (ccRCC) is a common type of kidney cancer and accounts for 2-3% of all cancer cases. Furthermore, a growing number of immunotherapy approaches are being used in antitumor treatment. Signaling lymphocyte activation molecule family (SLAMF) members have been well studied in several cancers, whereas their roles in ccRCC have not been investigated. The present study comprehensively assessed the molecular mechanisms of SLAMF members in ccRCC, performed using The Cancer Genome Atlas database, with analysis of gene transcription, prognosis, biological function, clinical features, tumor-associated immune cells and the correlation with programmed cell death protein 1/programmed death-ligand 1 immune checkpoints. Simultaneously, the Tumor Immune Dysfunction and Exclusion algorithm was used to predict the efficacy of immune checkpoint blockade (ICB) therapy in patients with high and low SLAMF expression levels. The results demonstrated that all SLAMF members were highly expressed in ccRCC, and patients with high expression levels of SLAMF1, 4, 7 and 8 had a worse prognosis that those with low expression. SLAMF members were not only highly associated with immune activation but also with immunosuppressive agents. The level of immune cell infiltration was associated with the prognosis of patients with ccRCC with high SLAMF expression. Moreover, high ICB response rates were observed in patients with high expression levels of SMALF1 and 4. In summary, SLAMF members may serve as future potential biomarkers for predicting the prognosis of ccRCC and emerge as a novel immunotherapy target.
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Affiliation(s)
- Na Song
- Department of Pathology, Xinxiang Key Laboratory of Tumor Precision Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Ziwei Wang
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Pingyu Shi
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Kai Cui
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Yanwu Fan
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Liqun Zeng
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
| | - Wenyu Di
- Department of Pathology, Xinxiang Key Laboratory of Tumor Precision Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
| | - Jinsong Li
- Department of Pathology, Xinxiang Key Laboratory of Tumor Precision Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
| | - Wei Su
- Department of Pathology, Xinxiang Key Laboratory of Tumor Precision Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
| | - Haijun Wang
- Department of Pathology, Xinxiang Key Laboratory of Tumor Precision Medicine, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
- Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China
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11
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Kyoda Y, Shibamori K, Shindo T, Maehana T, Hashimoto K, Kobayashi K, Tanaka T, Fukuta F, Masumori N. Intrinsic and extrinsic factors causing hyperplasia of the prostate. Int J Urol 2024; 31:705-717. [PMID: 38462732 PMCID: PMC11524118 DOI: 10.1111/iju.15446] [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] [Accepted: 02/20/2024] [Indexed: 03/12/2024]
Abstract
Prostatic hyperplasia is very common in elderly men and is a typical disease that reduces quality of life. Histologically, hyperplasia of the prostate gland causes obstruction at the bladder outlet, resulting in symptoms such as a weak urine stream. Various factors have been considered to cause histological enlargement of the prostate, but the underlying cause is still unknown. The factors that cause prostate hyperplasia can be broadly classified into intrinsic and extrinsic ones. Extrinsic factors include things that we directly come into contact with such as bacteria and food. On the other hand, intrinsic factors are those that cause changes in functions originally provided in the body due to some cause, including extrinsic factors, such as chronic inflammation and an imbalance of sex hormones. A large number of reports have been made to date regarding the etiology of prostatic hyperplasia, although they have not yet clarified the fundamental cause(s). The various factors currently known should be outlined for future research. Should it be possible to prevent this highly prevalent prostatic hyperplasia which is mainly cause of dcreasing quality of life, there is no doubt that it would be a huge contribution to humanity.
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Affiliation(s)
- Yuki Kyoda
- Department of UrologySapporo Medical University School of MedicineSapporoJapan
| | - Kosuke Shibamori
- Department of UrologySapporo Medical University School of MedicineSapporoJapan
| | - Tetsuya Shindo
- Department of UrologySapporo Medical University School of MedicineSapporoJapan
| | - Takeshi Maehana
- Department of UrologySapporo Medical University School of MedicineSapporoJapan
| | - Kohei Hashimoto
- Department of UrologySapporo Medical University School of MedicineSapporoJapan
| | - Ko Kobayashi
- Department of UrologySapporo Medical University School of MedicineSapporoJapan
| | - Toshiaki Tanaka
- Department of UrologySapporo Medical University School of MedicineSapporoJapan
| | - Fumimasa Fukuta
- Department of UrologySteel Memorial Muroran HospitalMuroranJapan
| | - Naoya Masumori
- Department of UrologySapporo Medical University School of MedicineSapporoJapan
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12
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He B, Hu Y, Cao Q, Li Y, Tang Y, Cao T, Zhou X, Liu S. Progression of unfolded protein response and ferroptosis in angiogenesis. Biomed Pharmacother 2024; 173:116354. [PMID: 38442673 DOI: 10.1016/j.biopha.2024.116354] [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: 11/01/2023] [Revised: 02/23/2024] [Accepted: 02/26/2024] [Indexed: 03/07/2024] Open
Abstract
Angiogenesis is the growth of new blood vessels on preexisting ones. It is the outcome of a multifactorial effect involving several cells, which can be brought on by different stress reactions.The accumulation of unfolded proteins in the endoplasmic reticulum occurs when cells are stressed due to environmental changes, where physical or chemical stimuli induce endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR), a homeostasis response designed to re-establish protein balance. Ferroptosis is a planned death of lipid peroxidation and anomalies in metabolism that is dependent on iron. Large concentrations of iron ions accumulate there, along with high concentrations of lipid peroxides and reactive oxygen species, all of which can contribute to the development of several diseases. Through the production of growth factors, adhesion factors, and inflammatory factors that trigger the start of angiogenesis, both UPR and Ferroptosis can be implicated in angiogenesis.To set the stage for further research on angiogenesis, this work concentrated on the effects of Ferroptosis and UPR on angiogenesis, respectively.
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Affiliation(s)
- Bisha He
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Yibao Hu
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Qian Cao
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Yue Li
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Yun Tang
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Ting Cao
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Xiangping Zhou
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
| | - Shuangquan Liu
- Department of Clinical Laboratory Medicine, Institution of microbiology and infectious diseases, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
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13
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He Q, Li C, Ou Y, Pan Y, Yang X, Wang J, Liao H, Xiong X, Liu L, Sun C. A novel NIR fluorescent probe inhibits melanoma progression through apoptosis and ERK/DRP1-mediated mitochondrial fission. Bioorg Chem 2024; 145:107218. [PMID: 38377820 DOI: 10.1016/j.bioorg.2024.107218] [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: 02/05/2024] [Accepted: 02/14/2024] [Indexed: 02/22/2024]
Abstract
Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. In vitro and in vivo experiments revealed IR-418's inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). Moreover, IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Notably, IR-418 mitigated abnormal ATL and ASL elevations caused by tumours without inflicting significant organ damage, indicating its high biocompatibility. In conclusion, IR-418, a novel hemicyanine-based NIR fluorescent probe targeting the mitochondria, exhibits significant fluorescence imaging capability, anti-melanoma proliferation, anti-melanoma lung metastasis activities and high biosafety. Therefore, it has significant potential in the early diagnosis and treatment of melanoma.
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Affiliation(s)
- Qingqing He
- Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China
| | - Changqiang Li
- Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China
| | - Yangrulan Ou
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China
| | - Yifan Pan
- Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China
| | - Xun Yang
- Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China
| | - Jianv Wang
- Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China
| | - Hongye Liao
- Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China
| | - Xia Xiong
- Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China
| | - Li Liu
- Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China.
| | - Changzhen Sun
- Drug Research Center of Integrated Traditional Chinese and Western Medicine, National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China.
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14
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Pan G, Xie H, Xia Y. Disulfidptosis characterizes the tumor microenvironment and predicts immunotherapy sensitivity and prognosis in bladder cancer. Heliyon 2024; 10:e25573. [PMID: 38356551 PMCID: PMC10864973 DOI: 10.1016/j.heliyon.2024.e25573] [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: 07/28/2023] [Revised: 01/13/2024] [Accepted: 01/29/2024] [Indexed: 02/16/2024] Open
Abstract
Background Bladder cancer (BLCA) is prone to metastasis and has poor prognosis with unsatisfactory treatment responsiveness. Disulfidptosis is a recently discovered, novel mode of cell death that is closely associated with human cancers. However, a comprehensive analysis of the relationship between disulfidptosis and BLCA is lacking. Therefore, this study aimed to explore the potential effect of disulfidptosis on BLCA and identify a biomarker for evaluating the prognosis and immunotherapy of patients with BLCA. Material and methods We acquired BLCA RNA sequencing data from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) cohort (containing 19 normal samples and 409 tumor samples) and the GES39281 cohort (containing 94 tumor samples) which were used for external validation of the signature. Initially, we performed unsupervised consensus clustering to explore disulfidptosis-related subgroups. We then conducted functional enrichment analysis on these subgroups to gain insights into their biological significance and evaluate their immunotherapy response and chemotherapy sensitivity. Next, we conducted Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate Cox regression to construct a prognostic signature in the TCGA training set for prognosis-related differentially expressed genes (DEGs) in the disulfidptosis-related subgroups. Subsequently, we used a receiver operating characteristic (ROC) curve and independent prognostic analysis to validate the predictive performance of the signature in the TCGA testing and the GES39281 cohorts. Finally, we explored the therapeutic value of this signature in patients with BLCA, in terms of immunotherapy and chemotherapy. Result In this study, we obtained two subgroups: DRG-high (238 samples) and DRG-low (160 samples). The DRG-high group exhibited a poor survival rate compared to the DRG-low group and had a significant association with tumor grade, stage, and metastasis. Additionally, several pathways related to cancer and the immune system were enriched in the high-DRG group. Moreover, the DRG-high group exhibited higher expression of PD1 and CTLA4 and had a better response to immunotherapy in patients with both PD1 and CTLA4 positivity. Conversely, the DRG-high group was more sensitive to common chemotherapeutic agents. A prognostic signature was created, consisting of COL5A1, DIRAS3, NKG7, and POLR3G and validated as having a robust predictive capability. Patients in the low-risk-score group had more immune cells associated with tumor suppression and better immunotherapy outcomes. Conclusion This study contributes to our understanding of the characteristics of disulfidptosis-related subgroups in BLCA. Disulfidptosis-related signatures can be used to assess the prognosis and immunotherapy of patients with BLCA.
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Affiliation(s)
- Guizhen Pan
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Huan Xie
- Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Yeye Xia
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Oncology, Chengdu Fifth People's Hospital, Sichuan, China
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15
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Yayan J, Franke KJ, Berger M, Windisch W, Rasche K. Adhesion, metastasis, and inhibition of cancer cells: a comprehensive review. Mol Biol Rep 2024; 51:165. [PMID: 38252369 PMCID: PMC10803487 DOI: 10.1007/s11033-023-08920-5] [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: 08/25/2023] [Accepted: 10/23/2023] [Indexed: 01/23/2024]
Abstract
This comprehensive review delves into cancer's complexity, focusing on adhesion, metastasis, and inhibition. It explores the pivotal role of these factors in disease progression and therapeutic strategies. This review covers cancer cell migration, invasion, and colonization of distant organs, emphasizing the significance of cell adhesion and the intricate metastasis process. Inhibition approaches targeting adhesion molecules, such as integrins and cadherins, are discussed. Overall, this review contributes significantly to advancing cancer research and developing targeted therapies, holding promise for improving patient outcomes worldwide. Exploring different inhibition strategies revealed promising therapeutic targets to alleviate adhesion and metastasis of cancer cells. The effectiveness of integrin-blocking antibodies, small molecule inhibitors targeting Focal adhesion kinase (FAK) and the Transforming Growth Factor β (TGF-β) pathway, and combination therapies underscores their potential to disrupt focal adhesions and control epithelial-mesenchymal transition processes. The identification of as FAK, Src, β-catenin and SMAD4 offers valuable starting points for further research and the development of targeted therapies. The complex interrelationships between adhesion and metastatic signaling networks will be relevant to the development of new treatment approaches.
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Affiliation(s)
- Josef Yayan
- Department of Internal Medicine, Division of Pulmonary, Allergy, and Sleep Medicine, Witten/Herdecke University, HELIOS Clinic Wuppertal, Heusnerstr. 40, 42283, Wuppertal, Germany.
| | - Karl-Josef Franke
- Department of Internal Medicine, Pulmonary Division, Internal Intensive Care Medicine, Infectiology, and Sleep Medicine, Märkische Clinics Health Holding Ltd, Clinic Lüdenscheid, Witten/Herdecke University, Lüdenscheid, Germany
| | - Melanie Berger
- Department of Pneumology, Cologne Merheim Hospital, Witten/Herdecke University, Cologne, Germany
| | - Wolfram Windisch
- Department of Pneumology, Cologne Merheim Hospital, Witten/Herdecke University, Cologne, Germany
| | - Kurt Rasche
- Department of Internal Medicine, Division of Pulmonary, Allergy, and Sleep Medicine, Witten/Herdecke University, HELIOS Clinic Wuppertal, Heusnerstr. 40, 42283, Wuppertal, Germany
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16
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Desai N, Katare P, Makwana V, Salave S, Vora LK, Giri J. Tumor-derived systems as novel biomedical tools-turning the enemy into an ally. Biomater Res 2023; 27:113. [PMID: 37946275 PMCID: PMC10633998 DOI: 10.1186/s40824-023-00445-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 10/11/2023] [Indexed: 11/12/2023] Open
Abstract
Cancer is a complex illness that presents significant challenges in its understanding and treatment. The classic definition, "a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body," fails to convey the intricate interaction between the many entities involved in cancer. Recent advancements in the field of cancer research have shed light on the role played by individual cancer cells and the tumor microenvironment as a whole in tumor development and progression. This breakthrough enables the utilization of the tumor and its components as biological tools, opening new possibilities. This article delves deeply into the concept of "tumor-derived systems", an umbrella term for tools sourced from the tumor that aid in combatting it. It includes cancer cell membrane-coated nanoparticles (for tumor theranostics), extracellular vesicles (for tumor diagnosis/therapy), tumor cell lysates (for cancer vaccine development), and engineered cancer cells/organoids (for cancer research). This review seeks to offer a complete overview of the tumor-derived materials that are utilized in cancer research, as well as their current stages of development and implementation. It is aimed primarily at researchers working at the interface of cancer biology and biomedical engineering, and it provides vital insights into this fast-growing topic.
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Affiliation(s)
- Nimeet Desai
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Pratik Katare
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Vaishali Makwana
- Center for Interdisciplinary Programs, Indian Institute of Technology Hyderabad, Kandi, Telangana, India
| | - Sagar Salave
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), Gujarat, India
| | - Lalitkumar K Vora
- School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
| | - Jyotsnendu Giri
- Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Telangana, India.
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17
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Odarenko KV, Salomatina OV, Chernikov IV, Salakhutdinov NF, Zenkova MA, Markov AV. Soloxolone Methyl Reduces the Stimulatory Effect of Leptin on the Aggressive Phenotype of Murine Neuro2a Neuroblastoma Cells via the MAPK/ERK1/2 Pathway. Pharmaceuticals (Basel) 2023; 16:1369. [PMID: 37895840 PMCID: PMC10610011 DOI: 10.3390/ph16101369] [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: 08/21/2023] [Revised: 09/25/2023] [Accepted: 09/25/2023] [Indexed: 10/29/2023] Open
Abstract
Despite the proven tumorigenic effect of leptin on epithelial-derived cancers, its impact on the aggressiveness of neural crest-derived cancers, notably neuroblastoma, remains largely unexplored. In our study, for the first time, transcriptome analysis of neuroblastoma tissue demonstrated that the level of leptin is elevated in neuroblastoma patients along with the severity of the disease and is inversely correlated with patient survival. The treatment of murine Neuro2a neuroblastoma cells with leptin significantly stimulated their proliferation and motility and reduced cell adhesion, thus rendering the phenotype of neuroblastoma cells more aggressive. Given the proven efficacy of cyanoenone-bearing semisynthetic triterpenoids in inhibiting the growth of neuroblastoma and preventing obesity in vivo, the effect of soloxolone methyl (SM) on leptin-stimulated Neuro2a cells was further investigated. We found that SM effectively abolished leptin-induced proliferation of Neuro2a cells by inducing G1/S cell cycle arrest and restored their adhesiveness to extracellular matrix (ECM) proteins to near control levels through the upregulation of vimentin, zonula occludens protein 1 (ZO-1), cell adhesion molecule L1 (L1cam), and neural cell adhesion molecule 1 (Ncam1). Moreover, SM significantly suppressed the leptin-associated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and ribosomal protein S6 kinase A1 (p90RSK), which are key kinases that ensure the survival and proliferation of cancer cells. Further molecular modeling studies demonstrated that the inhibitory effect of SM on the mitogen-activated protein kinase (MAPK)/ERK1/2 signaling pathway can be mediated by its direct interaction with ERK2 and its upstream regulators, son of sevenless homolog 1 (SOS) and mitogen-activated protein kinase kinase 1 (MEK1). Taken together, our findings in murine Neuro2a cells provide novel evidence of the stimulatory effect of leptin on the aggressiveness of neuroblastoma, which requires further detailed studies in human neuroblastoma cells and relevant animal models. The obtained results indicate that SM can be considered a promising drug candidate capable of reducing the impact of adipokines on tumor progression.
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Affiliation(s)
- Kirill V. Odarenko
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (K.V.O.); (O.V.S.); (I.V.C.); (M.A.Z.)
| | - Oksana V. Salomatina
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (K.V.O.); (O.V.S.); (I.V.C.); (M.A.Z.)
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia;
| | - Ivan V. Chernikov
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (K.V.O.); (O.V.S.); (I.V.C.); (M.A.Z.)
| | - Nariman F. Salakhutdinov
- N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia;
| | - Marina A. Zenkova
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (K.V.O.); (O.V.S.); (I.V.C.); (M.A.Z.)
| | - Andrey V. Markov
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; (K.V.O.); (O.V.S.); (I.V.C.); (M.A.Z.)
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Zhang Y, Zhao L, Bi Y, Zhao J, Gao C, Si X, Dai H, Asmamaw MD, Zhang Q, Chen W, Liu H. The role of lncRNAs and exosomal lncRNAs in cancer metastasis. Biomed Pharmacother 2023; 165:115207. [PMID: 37499455 DOI: 10.1016/j.biopha.2023.115207] [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: 06/09/2023] [Revised: 07/17/2023] [Accepted: 07/18/2023] [Indexed: 07/29/2023] Open
Abstract
Tumor metastasis is the main reason for cancer-related death, but there is still a lack of effective therapeutic to inhibit tumor metastasis. Therefore, the discovery and study of new tumor metastasis regulators is a prominent measure for cancer diagnosis and treatment. Long non-coding RNA (lncRNA) is a type of non-coding RNAs over 200 bp in length. It has been shown that the abnormally expressed lncRNAs promote tumor metastasis by participating in the epithelial-to-mesenchymal transition (EMT) process, altering the metastatic tumor microenvironment, or changing the extracellular matrix. It is,thus, critical to explore the regulation of lncRNAs expression in cells and the molecular mechanism of lncRNA-mediated cancer metastasis. Simultaneously, it has been shown that lncRNA is one kind of the main components of exosomes, which protects lncRNAs from being rapidly degraded. Meanwhile, the components of exosomes are parent-specific, making exosomal lncRNAs to be potential tumor metastasis markers and therapeutic targets. In view of this, we also summarized the aberrant enrichment of lncRNAs in exosomes and their role in metastatic cancer. The aberrant lncRNAs and exosomal lncRNAs gradually become biomarkers and therapeutic targets for tumor metastatic, and the potential of lncRNAs in therapeutics are studied here. Besides, the lncRNA-related databases, which could greatly facilitate in the study of lncRNAs and exosomal lncRNAs in metastatic of cancer are included in this review.
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Affiliation(s)
- Yutong Zhang
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China; The People's Hospital of Zhang Dian District, Zibo, China
| | - Lijuan Zhao
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Academy of Medical Science, Zhengzhou University, Zhengzhou China
| | - Yaping Bi
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China
| | - Jinyuan Zhao
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China
| | - Chao Gao
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China
| | - Xiaojie Si
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China
| | - Honglin Dai
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China
| | - Moges Dessale Asmamaw
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China
| | - Qiurong Zhang
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China.
| | - Wenchao Chen
- Department of Gastrointestinal Surgery, Henan Provincial People's Hospital; Zhengzhou University People's Hospital; Henan University People's Hospital, Zhengzhou China.
| | - Hongmin Liu
- State Key Laboratory of Esophageal Cancer Prevention & Treatment, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou China.
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Pimenta J, Pires I, Prada J, Cotovio M. E-Cadherin Immunostaining in Equine Melanocytic Tumors. Animals (Basel) 2023; 13:2216. [PMID: 37444014 DOI: 10.3390/ani13132216] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 06/30/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
Melanocytic tumors are an important neoplastic disease in human and veterinary medicine, presenting large differences regarding tumor behavior between species. In horses, these tumors present a prolonged benign behavior, with rare invasiveness and metastases. In humans and small animals, invasion and metastasis have been associated with an Epithelial-Mesenchymal Transition, where the loss of E-cadherin expression plays a key role in tumor progression. This process and the role of E-cadherin have not yet been evaluated in equine melanocytic tumors. This study aimed to assess the immunolabeling of E-cadherin in equine melanocytic tumors and relate this with clinicopathological variables. A total of 72 equine melanocytic tumors were classified as benign and malignant and evaluated by immunohistochemistry for E-cadherin expression. A different pattern of immunostaining was found, contrasting with other species. A total of 69.4% of tumors presented raised immunolabeling of E-cadherin, with 70.7% of melanomas remaining with high expression. The typical loss of immunostaining was not seen in malignant melanomas and no differences were found between benign and malignant melanomas regarding E-cadherin immunostaining. The high immunolabeling of E-cadherin may contribute to the low invasiveness of these tumors, and it is in accordance with the benign behavior of equine melanoma and with the genetic factors associated with its development.
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Affiliation(s)
- José Pimenta
- Veterinary Sciences Department, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
- CECAV-Veterinary and Animal Research Center, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 5000-801 Vila Real, Portugal
| | - Isabel Pires
- Veterinary Sciences Department, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
- CECAV-Veterinary and Animal Research Center, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 5000-801 Vila Real, Portugal
| | - Justina Prada
- Veterinary Sciences Department, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
- CECAV-Veterinary and Animal Research Center, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 5000-801 Vila Real, Portugal
| | - Mário Cotovio
- Veterinary Sciences Department, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
- CECAV-Veterinary and Animal Research Center, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 5000-801 Vila Real, Portugal
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Yao W, Yao Y, He W, Zhao C, Liu D, Wang G, Wang Z. PABPC1 promotes cell proliferation and metastasis in pancreatic adenocarcinoma by regulating COL12A1 expression. Immun Inflamm Dis 2023; 11:e919. [PMID: 37506150 PMCID: PMC10336663 DOI: 10.1002/iid3.919] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND The expression of cytoplasmic poly (A) binding protein-1 (PABPC1) has been reported in multiple cancer types. This protein is known to modulate cancer progression. However, the effects of PABPC1 expression in pancreatic adenocarcinoma (PAAD) have not been investigated. Here, we investigate the regulatory targets and molecular mechanisms of PABPC1 in PAAD. METHODS PABPC1 and collagen type XII α1 chain (COL12A1) expression in PAAD and their role in tumor prognosis and tumor stage were investigated using The Cancer Genome Atlas database analysis. After silencing PABPC1, messenger RNA sequencing and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The expression of differentially expressed genes (DEGs), cell viability, apoptosis, and cell migration and invasion were explored using reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry assay, and transwell assay, respectively. The relationship between PABPC1 and COL12A1 expression was assessed by Pearson's correlation analysis. The regulatory function of COL12A1 in PABPC1-affected BXPC3 cell behavior was studied after COL12A1 was overexpressed. RESULTS PABPC1 and COL12A1 expression was upregulated in patients with PAAD and was linked to poor prognosis. Four hundred and seventy-four DEGs were observed in BXPC3 cells after PABPC1 silencing. GO and KEGG analyses revealed that the top 10 DEGs were enriched in cell adhesion pathways. Additionally, PABPC1 silencing inhibited cell viability, migration, and invasion and accelerated apoptosis in BXPC3 cells. PABPC1 silencing increased AZGP1 and ARHGAP30 expression and decreased CAV1 and COL12A1 expression in BXPC3 cells. PABPC1 positively mediated COL12A1 expression, whereas PABPC1 knockdown induced the inhibition of BXPC3 cell proliferation, migration, and invasion. CONCLUSION The results of this study indicate that PABPC1 may function as a tumor promoter in PAAD, accelerating BXPC3 cell proliferation and metastasis by regulating COL12A1 expression.
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Affiliation(s)
- Weijie Yao
- Department of Hepatobiliary SurgeryGeneral Hospital of Ningxia Medical UniversityYinchuanChina
| | - Yanrong Yao
- Department of Hepatobiliary SurgeryGeneral Hospital of Ningxia Medical UniversityYinchuanChina
| | - Wen He
- Department of Hepatobiliary SurgeryGeneral Hospital of Ningxia Medical UniversityYinchuanChina
| | - Chengsi Zhao
- Department of Hepatobiliary SurgeryGeneral Hospital of Ningxia Medical UniversityYinchuanChina
| | - Di Liu
- Department of Hepatobiliary SurgeryGeneral Hospital of Ningxia Medical UniversityYinchuanChina
| | - Genwang Wang
- Department of Hepatobiliary SurgeryGeneral Hospital of Ningxia Medical UniversityYinchuanChina
| | - Zuozheng Wang
- Department of Hepatobiliary SurgeryGeneral Hospital of Ningxia Medical UniversityYinchuanChina
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21
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Ekeuku SO, Etim EP, Pang KL, Chin KY, Mai CW. Vitamin E in the management of pancreatic cancer: A scoping review. World J Gastrointest Oncol 2023; 15:943-958. [PMID: 37389119 PMCID: PMC10302993 DOI: 10.4251/wjgo.v15.i6.943] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 02/03/2023] [Accepted: 04/07/2023] [Indexed: 06/14/2023] Open
Abstract
Pancreatic cancer is the leading cause of cancer mortality worldwide. Research investigating effective management strategies for pancreatic cancer is ongoing. Vitamin E, consisting of both tocopherol and tocotrienol, has demonstrated debatable effects on pancreatic cancer cells. Therefore, this scoping review aims to summarize the effects of vitamin E on pancreatic cancer. In October 2022, a literature search was conducted using PubMed and Scopus since their inception. Original studies on the effects of vitamin E on pancreatic cancer, including cell cultures, animal models and human clinical trials, were considered for this review. The literature search found 75 articles on this topic, but only 24 articles met the inclusion criteria. The available evidence showed that vitamin E modulated proliferation, cell death, angiogenesis, metastasis and inflammation in pancreatic cancer cells. However, the safety and bioavailability concerns remain to be answered with more extensive preclinical and clinical studies. More in-depth analysis is necessary to investigate further the role of vitamin E in the management of pancreatic cancers.
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Affiliation(s)
- Sophia Ogechi Ekeuku
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Effiong Paul Etim
- Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
| | - Kok-Lun Pang
- Newcastle University Medicine Malaysia, Iskandar Puteri 79200, Johor, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Chun-Wai Mai
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
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22
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Wang H, Xu X, Wang Y, Xue X, Guo W, Guo S, Qiu S, Cui J, Qiao Y. NMT1 sustains ICAM-1 to modulate adhesion and migration of tumor cells. Cell Signal 2023:110739. [PMID: 37269961 DOI: 10.1016/j.cellsig.2023.110739] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 04/17/2023] [Accepted: 05/27/2023] [Indexed: 06/05/2023]
Abstract
Protein modifications have significant effects on tumorigenesis. N-Myristoylation is one of the most important lipidation modifications, and N-myristoyltransferase 1 (NMT1) is the main enzyme required for this process. However, the mechanism underlying how NMT1 modulates tumorigenesis remains largely unclear. Here, we found that NMT1 sustains cell adhesion and suppresses tumor cell migration. Intracellular adhesion molecule 1 (ICAM-1) was a potential functional downstream effector of NMT1, and its N-terminus could be N-myristoylated. NMT1 prevented ubiquitination and proteasome degradation of ICAM-1 by inhibiting Ub E3 ligase F-box protein 4, which prolonged the half-life of ICAM1 protein. Correlations between NMT1 and ICAM-1 were observed in liver and lung cancers, which were associated with metastasis and overall survival. Therefore, carefully designed strategies focusing on NMT1 and its downstream effectors might be helpful to treat tumors.
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Affiliation(s)
- Hong Wang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Xin Xu
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China
| | - Yikun Wang
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China
| | - Xiangfei Xue
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China
| | - Wanxin Guo
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China
| | - Susu Guo
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China
| | - Shiyu Qiu
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China
| | - Jiangtao Cui
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 200030, China
| | - Yongxia Qiao
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
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23
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Abstract
The genomics and pathways governing metastatic dormancy are critically important drivers of long-term patient survival given the considerable portion of cancers that recur aggressively months to years after initial treatments. Our understanding of dormancy has expanded greatly in the last two decades, with studies elucidating that the dormant state is regulated by multiple genes, microenvironmental (ME) interactions, and immune components. These forces are exerted through mechanisms that are intrinsic to the tumor cell, manifested through cross-talk between tumor and ME cells including those from the immune system, and regulated by angiogenic processes in the nascent micrometastatic niche. The development of new in vivo and 3D ME models, as well as enhancements to decades-old tumor cell pedigree models that span the development of metastatic dormancy to aggressive growth, has helped fuel what arguably is one of the least understood areas of cancer biology that nonetheless contributes immensely to patient mortality. The current review focuses on the genes and molecular pathways that regulate dormancy via tumor-intrinsic and ME cells, and how groups have envisioned harnessing these therapeutically to benefit patient survival.
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24
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Liu J, Zhang J, Fu X, Yang S, Li Y, Liu J, DiSanto ME, Chen P, Zhang X. The Emerging Role of Cell Adhesion Molecules on Benign Prostatic Hyperplasia. Int J Mol Sci 2023; 24:2870. [PMID: 36769190 PMCID: PMC9917596 DOI: 10.3390/ijms24032870] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 01/01/2023] [Accepted: 01/18/2023] [Indexed: 02/05/2023] Open
Abstract
Benign prostatic hyperplasia (BPH) is a common disease in elderly men. It is characterized by prostatic enlargement and urethral compression and often causes lower urinary tract symptoms (LUTs) such as urinary frequency, urgency, and nocturia. Existing studies have shown that the pathological process of prostate hyperplasia is mainly related to the imbalance of cell proliferation and apoptosis, inflammation, epithelial-mesenchymal transition (EMT), and growth factors. However, the exact molecular mechanisms remain incompletely elucidated. Cell adhesion molecules (CAMs) are a group of cell surface proteins that mediate cell-cell adhesion and cell migration. Modulating adhesion molecule expression can regulate cell proliferation, apoptosis, EMT, and fibrotic processes, engaged in the development of prostatic hyperplasia. In this review, we went over the important roles and molecular mechanisms of cell adhesion molecules (mainly integrins and cadherins) in both physiological and pathological processes. We also analyzed the mechanisms of CAMs in prostate hyperplasia and explored the potential value of targeting CAMs as a therapeutic strategy for BPH.
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Affiliation(s)
- Jiang Liu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Junchao Zhang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Xun Fu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Shu Yang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Yan Li
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Jianmin Liu
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Michael E. DiSanto
- Department of Surgery and Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA
| | - Ping Chen
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Xinhua Zhang
- Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
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25
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Niu ZS, Wang WH, Niu XJ. Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma. World J Gastroenterol 2022; 28:6433-6477. [PMID: 36569275 PMCID: PMC9782839 DOI: 10.3748/wjg.v28.i46.6433] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 10/31/2022] [Accepted: 11/21/2022] [Indexed: 12/08/2022] Open
Abstract
Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma (HCC). Unfortunately, the postoperative prognosis of patients with HCC remains unsatisfactory, predominantly because of high postoperative metastasis and recurrence rates. Therefore, research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients. Herein, we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.
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Affiliation(s)
- Zhao-Shan Niu
- Laboratory of Micromorphology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Wen-Hong Wang
- Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Xiao-Jun Niu
- Department of Internal Medicine, Qingdao Shibei District People's Hospital, Qingdao 266033, Shandong Province, China
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26
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Li J, Li X, Guo Q. Drug Resistance in Cancers: A Free Pass for Bullying. Cells 2022; 11:3383. [PMID: 36359776 PMCID: PMC9654341 DOI: 10.3390/cells11213383] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/13/2022] [Accepted: 10/20/2022] [Indexed: 08/13/2023] Open
Abstract
The cancer burden continues to grow globally, and drug resistance remains a substantial challenge in cancer therapy. It is well established that cancerous cells with clonal dysplasia generate the same carcinogenic lesions. Tumor cells pass on genetic templates to subsequent generations in evolutionary terms and exhibit drug resistance simply by accumulating genetic alterations. However, recent evidence has implied that tumor cells accumulate genetic alterations by progressively adapting. As a result, intratumor heterogeneity (ITH) is generated due to genetically distinct subclonal populations of cells coexisting. The genetic adaptive mechanisms of action of ITH include activating "cellular plasticity", through which tumor cells create a tumor-supportive microenvironment in which they can proliferate and cause increased damage. These highly plastic cells are located in the tumor microenvironment (TME) and undergo extreme changes to resist therapeutic drugs. Accordingly, the underlying mechanisms involved in drug resistance have been re-evaluated. Herein, we will reveal new themes emerging from initial studies of drug resistance and outline the findings regarding drug resistance from the perspective of the TME; the themes include exosomes, metabolic reprogramming, protein glycosylation and autophagy, and the relates studies aim to provide new targets and strategies for reversing drug resistance in cancers.
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Affiliation(s)
| | | | - Qie Guo
- The Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
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27
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Baqai U, Purwin TJ, Bechtel N, Chua V, Han A, Hartsough EJ, Kuznetsoff JN, Harbour JW, Aplin AE. Multi-omics profiling shows BAP1 loss is associated with upregulated cell adhesion molecules in uveal melanoma. Mol Cancer Res 2022; 20:1260-1271. [DOI: 10.1158/1541-7786.mcr-21-0657] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 02/04/2022] [Accepted: 04/11/2022] [Indexed: 11/16/2022]
Abstract
Abstract
BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is mutated in cancer, including uveal melanoma (UM). Loss-of-function BAP1 mutations are associated with UM metastasis and poor prognosis, but the mechanisms underlying these effects remain unclear. Upregulation of cell-cell adhesion proteins is involved with collective migration and metastatic seeding of cancer cells. Here, we show that BAP1 loss in UM patient samples is associated with upregulated gene expression of multiple cell adhesion molecules (CAMs), including E-cadherin (CDH1), cell adhesion molecule 1 (CADM1), and syndecan-2 (SDC2). Similar findings were observed in UM cell lines and scRNA seq data from UM patient samples. BAP1 re-expression in UM cells reduced E-cadherin and CADM1 levels. Functionally, knockdown of E-cadherin decreased spheroid cluster formation and knockdown of CADM1 decreased growth of BAP1 mutant UM cells. Together, our findings demonstrate that BAP1 regulates the expression of CAMs which may regulate metastatic traits. Implications: BAP1 mutations and increased metastasis may be due to upregulation of cell adhesion molecules.
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Affiliation(s)
- Usman Baqai
- Thomas Jefferson University, Philadelphia, PA, United States
| | | | - Nelisa Bechtel
- Thomas Jefferson University, Philadelphia, PA, United States
| | - Vivian Chua
- Thomas Jefferson University, Philadelphia, PA, United States
| | - Anna Han
- Thomas Jefferson University, Philadelphia, PA, United States
| | - Edward J. Hartsough
- Drexel University College of Medicine, Philadelphia, Pennsylvania, United States
| | | | | | - Andrew E. Aplin
- Thomas Jefferson University, Philadelphia, PA, United States
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28
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HDACs and the epigenetic plasticity of cancer cells: Target the complexity. Pharmacol Ther 2022; 238:108190. [PMID: 35430294 DOI: 10.1016/j.pharmthera.2022.108190] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 04/07/2022] [Accepted: 04/11/2022] [Indexed: 12/11/2022]
Abstract
Cancer cells must adapt to the hostile conditions of the microenvironment in terms of nutrition, space, and immune system attack. Mutations of DNA are the drivers of the tumorigenic process, but mutations must be able to hijack cellular functions to sustain the spread of mutant genomes. Transcriptional control is a key function in this context and is controlled by the rearrangement of the epigenome. Unlike genomic mutations, the epigenome of cancer cells can in principle be reversed. The discovery of the first epigenetic drugs triggered a contaminating enthusiasm. Unfortunately, the complexity of the epigenetic machinery has frustrated this enthusiasm. To develop efficient patient-oriented epigenetic therapies, we need to better understand the nature of this complexity. In this review, we will discuss recent advances in understanding the contribution of HDACs to the maintenance of the transformed state and the rational for their selective targeting.
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29
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Guo S, Li T, Xu D, Xu J, Wang H, Li J, Bi X, Cao M, Xu Z, Xia Q, Cui Y, Li K. Prognostic Implications and Immune Infiltration Characteristics of Chromosomal Instability-Related Dysregulated CeRNA in Lung Adenocarcinoma. Front Mol Biosci 2022; 9:843640. [PMID: 35419410 PMCID: PMC8995899 DOI: 10.3389/fmolb.2022.843640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 02/22/2022] [Indexed: 12/14/2022] Open
Abstract
An accumulating body of research indicates that long-noncoding RNAs (lncRNAs) regulate the target genes and act as competitive endogenous RNAs (ceRNAs) playing an indispensable role in lung adenocarcinoma (LUAD). LUAD is frequently accompanied by the feature of chromosomal instability (CIN); however, CIN-related ceRNAs have not been investigated yet. We systematically analyzed and integrated CIN-related dysregulated ceRNAs characteristics in LUAD samples for the first time. In TCGA LUAD cohort, CIN in tumor samples was significantly higher than that in those of adjacent, and patients with high CIN risk tended to have worse clinical outcomes. We constructed a double-weighted CIN-related dysregulated ceRNA network, in which edge weight and node weight represented the disorder extent of ceRNA and the correlation of RNA expression level and prognosis, respectively. After module mining and analysis, a potential prognostic biomarker composed of 12 RNAs (8 mRNAs and 4 lncRNAs) named CIN-related dysregulated ceRNAs (CRDC) was obtained. The CRDC risk score had a positive relation with clinical stage and CIN, and patients with high CRDC risk scores exhibited poor prognosis. Moreover, CRDC tended to be an independent risk factor with high robustness to overcome the effect of multicollinearity among other explanatory variables for disease-specific survival (DSS) in TCGA and two GEO cohorts. The result of functional analysis indicated that CRDC was involved in multiple cancer progresses, especially immune-related pathways. The patients with lower CRDC risk had higher B cell, T cell CD4+, T cell CD8+, neutrophil, macrophage, and myeloid dendritic cell infiltration than the patients with higher CRDC risk. Meanwhile, patients with lower CRDC risk could get more benefits from immunological therapy. The results suggested that the CRDC could be a potential prognostic biomarker and an immunotherapy predictor for lung adenocarcinoma.
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Affiliation(s)
- Shengnan Guo
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China
| | - Tianhao Li
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China
| | - Dahua Xu
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China
| | - Jiankai Xu
- College of Bioinformatics Science and Technology, Cancer Hospital, Harbin Medical University, Harbin, China
| | - Hong Wang
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China
| | - Jian Li
- College of Bioinformatics Science and Technology, Cancer Hospital, Harbin Medical University, Harbin, China
| | - Xiaoman Bi
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China
| | - Meng Cao
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China
| | - Zhizhou Xu
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China
| | - Qianfeng Xia
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, NHC Key Laboratory of Control of Tropical Diseases, School of Tropical Medicine, The Second Affiliated Hospital, Hainan Medical University, Haikou, China
- *Correspondence: Qianfeng Xia, ; Ying Cui, ; Kongning Li,
| | - Ying Cui
- College of Bioinformatics Science and Technology, Cancer Hospital, Harbin Medical University, Harbin, China
- *Correspondence: Qianfeng Xia, ; Ying Cui, ; Kongning Li,
| | - Kongning Li
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China
- *Correspondence: Qianfeng Xia, ; Ying Cui, ; Kongning Li,
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30
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Using ELP Repeats as a Scaffold for De Novo Construction of Gadolinium-Binding Domains within Multifunctional Recombinant Proteins for Targeted Delivery of Gadolinium to Tumour Cells. Int J Mol Sci 2022; 23:ijms23063297. [PMID: 35328725 PMCID: PMC8949254 DOI: 10.3390/ijms23063297] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/07/2022] [Accepted: 03/15/2022] [Indexed: 02/08/2023] Open
Abstract
Three artificial proteins that bind the gadolinium ion (Gd3+) with tumour-specific ligands were de novo engineered and tested as candidate drugs for binary radiotherapy (BRT) and contrast agents for magnetic resonance imaging (MRI). Gd3+-binding modules were derived from calmodulin. They were joined with elastin-like polypeptide (ELP) repeats from human elastin to form the four-centre Gd3+-binding domain (4MBS-domain) that further was combined with F3 peptide (a ligand of nucleolin, a tumour marker) to form the F3-W4 block. The F3-W4 block was taken alone (E2-13W4 protein), as two repeats (E1-W8) and as three repeats (E1-W12). Each protein was supplemented with three copies of the RGD motif (a ligand of integrin αvβ3) and green fluorescent protein (GFP). In contrast to Magnevist (a Gd-containing contrast agent), the proteins exhibited three to four times higher accumulation in U87MG glioma and A375 melanoma cell lines than in normal fibroblasts. The proteins remained for >24 h in tumours induced by Ca755 adenocarcinoma in C57BL/6 mice. They exhibited stability towards blood proteases and only accumulated in the liver and kidney. The technological advantages of using the engineered proteins as a basis for developing efficient and non-toxic agents for early diagnosis of tumours by MRI as well as part of BRT were demonstrated.
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31
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Liu Z, Wang H, Sun C, He Y, Xia T, Wang J, Xiong X, Zhang Q, Yang S, Liu L. ZWZ-3, a Fluorescent Probe Targeting Mitochondria for Melanoma Imaging and Therapy. Front Pharmacol 2022; 13:829684. [PMID: 35281928 PMCID: PMC8905922 DOI: 10.3389/fphar.2022.829684] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 01/24/2022] [Indexed: 12/16/2022] Open
Abstract
The increased drug resistance and metastasis of melanoma resulted in poor prognosis of patients. Here, we designed and synthesized a novel hemicyanine-based fluorescent probe ZWZ-3, and investigated its application for melanoma imaging and treatment both in vitro and in vivo. ZWZ-3 preferentially accumulated in melanoma cells via a process that depended on the organic anion-transporting polypeptide (OATP), which targeted mitochondria on the hemicyanine cationic nitrogen. In addition, we investigated the effect and molecular mechanism of ZWZ-3 in melanoma. In vitro studies showed that ZWZ-3 promoted the generation of reactive oxygen species and induced mitochondrial-mediated cell apoptosis by upregulating Bax and activating caspase-3, caspase-9, and PARP. Importantly, ZWZ-3 also induced autophagy by upregulating LC-3II and Atg5 and downregulating P62. It significantly suppressed tumor growth of A375 xenograft tumor in mice without notable side effects. Histological and immunohistochemical analyses revealed that ZWZ-3 induced apoptosis and inhibited tumor cell proliferation. Thus, ZWZ-3 represents a novel theranostic agent that can be used to effectively targeting, detecting, and treating melanoma. It could also help monitoring disease progression and response to treatment.
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Affiliation(s)
- Zengjin Liu
- National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Hailan Wang
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,School of Public Health, Southwest Medical University, Luzhou, China
| | - Changzhen Sun
- National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Yuanmin He
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Tong Xia
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jianv Wang
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xia Xiong
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Qingbi Zhang
- School of Public Health, Southwest Medical University, Luzhou, China
| | - Sijin Yang
- National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China
| | - Li Liu
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
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32
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Guo F, Liu Y, Cheng Y, Zhang Q, Quan W, Wei Y, Hong L. Transcriptome analysis reveals the potential biological function of FSCN1 in HeLa cervical cancer cells. PeerJ 2022; 10:e12909. [PMID: 35178306 PMCID: PMC8817631 DOI: 10.7717/peerj.12909] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 01/19/2022] [Indexed: 01/11/2023] Open
Abstract
Fascin actin-bundling protein 1 (FSCN1), an actin-bundling protein associated with cell migration and invasion, is highly expressed in various tumor tissues. FSCN1 has also been reported to be a marker of increased invasive potential in cervical cancers. However, the functions of FSCN1 are still not fully understood in cervical cancers. Here, the gene expression profile of HeLa cells transfected with FSCN1 shRNA (shFSCN1) was compared with that of cells transfected with empty vector (shCtrl). The results showed that shFSCN1 extensively affected the transcription level of 5,043 genes in HeLa cells. In particular, Gene Ontology (GO) analysis showed that a large number of upregulated genes were annotated with terms including transcription regulation and DNA binding. The downregulated genes were enriched in some cancer pathways, including angiogenesis and cell adhesion. qPCR validation confirmed that FSCN1 knockdown significantly affected the expression of selected genes in HeLa cells either negatively or positively. Expression analysis in TCGA (The Cancer Genome Atlas) revealed that FSCN1 had negative correlations with several transcription factors and a positive correlation with an angiogenic factor (angiopoietin like 4, ANGPTL4) in cervical tumor tissue. In particular, validation by Western blotting showed that FSCN1 knockdown decreased the protein level of ANGPTL4. Our results demonstrated that FSCN1 is not only an actin-binding protein but also a transcriptional regulator and an angiogenic factor in cervical cancer. Thus, our study provides important insights for further study on the regulatory mechanism of FSCN1 in cervical cancer.
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Affiliation(s)
- Fengqin Guo
- Department of Obstetrics & Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Yanliang Liu
- Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Yanxiang Cheng
- Department of Obstetrics & Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Qifan Zhang
- Department of Obstetrics & Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
| | - Weili Quan
- ABLife BioBigData Institute, Wuhan, Hubei Province, China
| | - Yaxun Wei
- Center for Genome Analysis, ABLife Inc., Wuhan, Hubei Province, China
| | - Li Hong
- Department of Obstetrics & Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
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Takabe P, Siiskonen H, Rönkä A, Kainulainen K, Pasonen-Seppänen S. The Impact of Hyaluronan on Tumor Progression in Cutaneous Melanoma. Front Oncol 2022; 11:811434. [PMID: 35127523 PMCID: PMC8813769 DOI: 10.3389/fonc.2021.811434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 12/31/2021] [Indexed: 12/21/2022] Open
Abstract
The incidence of cutaneous melanoma is rapidly increasing worldwide. Cutaneous melanoma is an aggressive type of skin cancer, which originates from malignant transformation of pigment producing melanocytes. The main risk factor for melanoma is ultraviolet (UV) radiation, and thus it often arises from highly sun-exposed skin areas and is characterized by a high mutational burden. In addition to melanoma-associated mutations such as BRAF, NRAS, PTEN and cell cycle regulators, the expansion of melanoma is affected by the extracellular matrix surrounding the tumor together with immune cells. In the early phases of the disease, hyaluronan is the major matrix component in cutaneous melanoma microenvironment. It is a high-molecular weight polysaccharide involved in several physiological and pathological processes. Hyaluronan is involved in the inflammatory reactions associated with UV radiation but its role in melanomagenesis is still unclear. Although abundant hyaluronan surrounds epidermal and dermal cells in normal skin and benign nevi, its content is further elevated in dysplastic lesions and local tumors. At this stage hyaluronan matrix may act as a protective barrier against melanoma progression, or alternatively against immune cell attack. While in advanced melanoma, the content of hyaluronan decreases due to altered synthesis and degradation, and this correlates with poor prognosis. This review focuses on hyaluronan matrix in cutaneous melanoma and how the changes in hyaluronan metabolism affect the progression of melanoma.
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Affiliation(s)
- Piia Takabe
- Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
| | - Hanna Siiskonen
- Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland
| | - Aino Rönkä
- Department of Oncology, Kuopio University Hospital, Kuopio, Finland
| | - Kirsi Kainulainen
- Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
| | - Sanna Pasonen-Seppänen
- Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
- *Correspondence: Sanna Pasonen-Seppänen,
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Abstract
Melanoma is the most lethal skin cancer that originates from the malignant transformation of melanocytes. Although melanoma has long been regarded as a cancerous malignancy with few therapeutic options, increased biological understanding and unprecedented innovations in therapies targeting mutated driver genes and immune checkpoints have substantially improved the prognosis of patients. However, the low response rate and inevitable occurrence of resistance to currently available targeted therapies have posed the obstacle in the path of melanoma management to obtain further amelioration. Therefore, it is necessary to understand the mechanisms underlying melanoma pathogenesis more comprehensively, which might lead to more substantial progress in therapeutic approaches and expand clinical options for melanoma therapy. In this review, we firstly make a brief introduction to melanoma epidemiology, clinical subtypes, risk factors, and current therapies. Then, the signal pathways orchestrating melanoma pathogenesis, including genetic mutations, key transcriptional regulators, epigenetic dysregulations, metabolic reprogramming, crucial metastasis-related signals, tumor-promoting inflammatory pathways, and pro-angiogenic factors, have been systemically reviewed and discussed. Subsequently, we outline current progresses in therapies targeting mutated driver genes and immune checkpoints, as well as the mechanisms underlying the treatment resistance. Finally, the prospects and challenges in the development of melanoma therapy, especially immunotherapy and related ongoing clinical trials, are summarized and discussed.
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Affiliation(s)
- Weinan Guo
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 of West Changle Road, 710032, Xi'an, Shaanxi, China
| | - Huina Wang
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 of West Changle Road, 710032, Xi'an, Shaanxi, China
| | - Chunying Li
- Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 of West Changle Road, 710032, Xi'an, Shaanxi, China.
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Bukhari SZ, Zeth K, Iftikhar M, Rehman M, Usman Munir M, Khan WS, Ihsan A. Supramolecular lipid nanoparticles as delivery carriers for non-invasive cancer theranostics. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2021; 2:100067. [PMID: 34909685 PMCID: PMC8663983 DOI: 10.1016/j.crphar.2021.100067] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/22/2021] [Accepted: 10/25/2021] [Indexed: 12/12/2022] Open
Abstract
Nanotheranostics is an emerging frontier of personalized medicine research particularly for cancer, which is the second leading cause of death. Supramolecular aspects in theranostics are quite allured to achieve more regulation and controlled features. Supramolecular nanotheranostics architecture is focused on engineering of modular supramolecular assemblies benefitting from their mutable and stimuli-responsive properties which confer an ultimate potential for the fabrication of unified innovative nanomedicines with controlled features. Amalgamation of supramolecular approaches to nano-based features further equip the potential of designing novel approaches to overcome limitations seen by the conventional theranostic strategies, for curing even the lethal diseases and endowing personalized therapeutics with optimistic prognosis, endorsing their clinical translation. Among many potential nanocarriers for theranostics, lipid nanoparticles (LNPs) have shown various promising advances in theranostics and their formulation can be tailored for several applications. Despite the great advancement in cancer nanotheranostics, there are still many challenges that need to be highlighted to fill the literature gap. For this purpose, herein, we have presented a systematic overview on the subject and proposed LNPs as the potential material to manage cancer via non-invasive approaches by highlighting the use of supramolecular approaches to make them robust for cancer theranostics. We have concluded the review by entailing the future perspectives of lipid nanotheranostics towards clinical translation.
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Affiliation(s)
- Syeda Zunaira Bukhari
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Kornelius Zeth
- Department of Science and Environment, Roskilde University Center, DK-4000 Roskilde, Denmark
| | - Maryam Iftikhar
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Mubashar Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muhammad Usman Munir
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Aljouf, 72388, Saudi Arabia
| | - Waheed S. Khan
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Ayesha Ihsan
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
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D’Arcy C, Kiel C. Cell Adhesion Molecules in Normal Skin and Melanoma. Biomolecules 2021; 11:biom11081213. [PMID: 34439879 PMCID: PMC8391223 DOI: 10.3390/biom11081213] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 08/10/2021] [Accepted: 08/11/2021] [Indexed: 12/11/2022] Open
Abstract
Cell adhesion molecules (CAMs) of the cadherin, integrin, immunoglobulin, and selectin protein families are indispensable for the formation and maintenance of multicellular tissues, especially epithelia. In the epidermis, they are involved in cell–cell contacts and in cellular interactions with the extracellular matrix (ECM), thereby contributing to the structural integrity and barrier formation of the skin. Bulk and single cell RNA sequencing data show that >170 CAMs are expressed in the healthy human skin, with high expression levels in melanocytes, keratinocytes, endothelial, and smooth muscle cells. Alterations in expression levels of CAMs are involved in melanoma propagation, interaction with the microenvironment, and metastasis. Recent mechanistic analyses together with protein and gene expression data provide a better picture of the role of CAMs in the context of skin physiology and melanoma. Here, we review progress in the field and discuss molecular mechanisms in light of gene expression profiles, including recent single cell RNA expression information. We highlight key adhesion molecules in melanoma, which can guide the identification of pathways and strategies for novel anti-melanoma therapies.
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