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Lei GL, Niu Y, Cheng SJ, Li YY, Bai ZF, Yu LX, Hong ZX, Liu H, Liu HH, Yan J, Gao Y, Zhang SG, Chen Z, Li RS, Yang PH. Upregulation of long noncoding RNA W42 promotes tumor development by binding with DBN1 in hepatocellular carcinoma. World J Gastroenterol 2021; 27:2586-2602. [PMID: 34092977 PMCID: PMC8160624 DOI: 10.3748/wjg.v27.i20.2586] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/10/2021] [Accepted: 04/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a malignancy found globally. Accumulating studies have shown that long noncoding RNAs (lncRNAs) play critical roles in HCC. However, the function of lncRNA in HCC remains poorly understood. AIM To understand the effect of lncRNA W42 on HCC and dissect the underlying molecular mechanisms. METHODS We measured the expression of lncRNA W42 in HCC tissues and cells (Huh7 and SMMC-7721) by quantitative reverse transcriptase polymerase chain reaction. Receiver operating characteristic curves were used to assess the sensitivity and specificity of lncRNA W42 expression. HCC cells were transfected with pcDNA3.1-lncRNA W42 or shRNA-lncRNA W42. Cell functions were detected by cell counting Kit-8 (CCK-8), colony formation, flow cytometry and Transwell assays. The interaction of lncRNA W42 and DBN1 was confirmed by RNA immunoprecipitation and RNA pull down assays. An HCC xenograft model was used to assess the role of lncRNA W42 on tumor growth in vivo. The Kaplan-Meier curve was used to evaluate the overall survival and recurrence-free survival after surgery in patients with HCC. RESULTS In this study, we identified a novel lncRNA (lncRNA W42), and investigated its biological functions and clinical significance in HCC. LncRNA W42 expression was upregulated in HCC tissues and cells. Overexpression of lncRNA W42 notably promoted the proliferative and invasion of HCC, and inhibited cell apoptosis. LncRNA W42 directly bound to DBN1 and activated the downstream pathway. LncRNA W42 knockdown suppressed HCC xenograft tumor growth in vivo. The clinical investigation revealed that HCC patients with high lncRNA W42 expression exhibited shorter survival times. CONCLUSION In vitro and in vivo results suggested that the novel lncRNA W42, which is upregulated in HCC, may serve as a potential candidate prognostic biomarker and therapeutic target in HCC patients.
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Affiliation(s)
- Guang-Lin Lei
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yan Niu
- Inner Mongolia Medical University, Hohhot 010110, Inner Mongolia Autonomous Region, China
| | - Si-Jie Cheng
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yuan-Yuan Li
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhi-Fang Bai
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Ling-Xiang Yu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhi-Xian Hong
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hu Liu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Hong-Hong Liu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Jin Yan
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yuan Gao
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Shao-Geng Zhang
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zhu Chen
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Rui-Sheng Li
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Peng-Hui Yang
- Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
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Cytometric analysis of cell suspension generated by cavitron ultrasonic surgical aspirator in pediatric brain tumors. J Neurooncol 2019; 143:15-25. [PMID: 30827009 DOI: 10.1007/s11060-019-03135-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 02/23/2019] [Indexed: 12/15/2022]
Abstract
PURPOSE The aim of this study was to test the possibility of using specimens obtained by a cavitron ultrasonic surgical aspirator (CUSA) in flow and mass cytometry investigations of pediatric brain tumors. METHODS CUSA specimens obtained from 19 pediatric patients with brain tumors were investigated. Flow and mass cytometry methods were applied to analyze the composition of material collected using the CUSA. Cell suspensions were prepared from CUSA aspirates. Then sample viability was assessed by conventional flow cytometry and subsequently stained with a panel of 31 metal-labeled antibodies. RESULTS Viability assessment was performed using conventional flow cytometry. Viability of cells in the acquired samples was below 50% in 16 of 19 cases. A mass cytometry investigation and subsequent analysis enabled us to discriminate brain tumor cells from contaminating leukocytes, whose proportions varied across the specimens. The addition of the viability marker cisplatin directly into the mass cytometry panel gave the means to selecting viable cells only for subsequent analyses. The proportion of non-viable cells was higher among tumor cells compared leukocytes. CONCLUSIONS When the analysis of the tumor cell immunophenotype is performed with markers for determining viability, the expression of the investigated markers can be evaluated. Suitable markers can be selected by high-throughput methods, such as mass cytometry, and those that are diagnostically relevant can be investigated using flow cytometry, which is more flexible in terms of time.
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Homer, Spikar, and Other Drebrin-Binding Proteins in the Brain. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 1006:249-268. [PMID: 28865024 DOI: 10.1007/978-4-431-56550-5_14] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Drebrin is a major F-actin-binding protein in the brain. In the past two decades, many drebrin-binding proteins in addition to F-actin have been identified in several research fields including neuroscience, oncology, and immunology. Among the drebrin-binding proteins, there are various kinds of proteins including scaffold proteins, nuclear proteins, phosphatases, microtubule-binding proteins, G-actin-binding proteins, gap junction proteins, chemokine receptors, and cell-adhesion-related proteins. The interaction between drebrin and its binding partners seems to play important roles in higher brain functions, because drebrin is involved in the pathogenesis of some neurological diseases with cognitive defects. In this chapter, we will first review the interaction of Homer and spikar with drebrin, particularly focusing on spine morphogenesis and synaptic function. Homer contributes to spine morphogenesis by cooperating with shank and activated Cdc42 small GTPase, suggesting a novel signaling pathway comprising Homer, drebrin, shank, and Cdc42 for spine morphogenesis. Drebrin sequesters spikar in the cytoplasm and stabilizes it in dendritic spines, leading to spine formation. Finally, we will introduce some other drebrin-binding proteins including end-binding protein 3 (EB3), profilin, progranulin, and phosphatase and tensin homologue (PTEN). These proteins are involved in Alzheimer's disease and cancer. Therefore, further studies on drebrin and its binding proteins will be of great importance to elucidate the pathologies of various diseases and may contribute to their medical treatment and diagnostics development.
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The Role of Drebrin in Cancer Cell Invasion. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 1006:375-389. [DOI: 10.1007/978-4-431-56550-5_23] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Role of Drebrin at the Immunological Synapse. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 1006:271-280. [PMID: 28865025 DOI: 10.1007/978-4-431-56550-5_15] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Although drebrin was first described in neurons, it is also expressed in cells of the immune system, such as T lymphocytes and mast cells. Another member of the drebrin family of proteins, mammalian actin-binding protein 1 (mAbp-1) is more widely expressed and plays important roles in the function of macrophages, polymorphonuclear neutrophils, and B lymphocytes. We will briefly discuss on the function of mAbp-1 and drebrin in immune cells with emphasis on T cells. Specifically, drebrin enables the immune responses of CD4+ T lymphocytes. T cells are activated after the recognition of an antigen presented by antigen-presenting cells through cognate cell-cell contacts called immunological synapses (IS). In CD4+ T cells, drebrin associates with the chemokine receptor CXCR4, and both molecules redistribute to the IS displaying similar dynamics. Through its interaction with CXCR4 and the actin cytoskeleton, drebrin regulates T cell activation. CD4+ T cells are one of the main targets for the human immunodeficiency virus (HIV)-1. This virus utilizes the IS structure to be transmitted to uninfected cells, forming cell-cell contacts called virological synapses (VS). Interestingly, drebrin negatively regulates HIV-1 infection of CD4+ T lymphocytes, by regulating actin polymerization at the VS.
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Lestanova Z, Puerta F, Alanazi M, Bacova Z, Kiss A, Castejon AM, Bakos J. Downregulation of Oxytocin Receptor Decreases the Length of Projections Stimulated by Retinoic Acid in the U-87MG Cells. Neurochem Res 2016; 42:1006-1014. [DOI: 10.1007/s11064-016-2133-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 11/03/2016] [Accepted: 12/03/2016] [Indexed: 12/24/2022]
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Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood 2016; 129:347-357. [PMID: 27903527 DOI: 10.1182/blood-2016-07-726307] [Citation(s) in RCA: 287] [Impact Index Per Article: 31.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 11/23/2016] [Indexed: 12/12/2022] Open
Abstract
A fully-standardized EuroFlow 8-color antibody panel and laboratory procedure was stepwise designed to measure minimal residual disease (MRD) in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) patients with a sensitivity of ≤10-5, comparable to real-time quantitative polymerase chain reaction (RQ-PCR)-based MRD detection via antigen-receptor rearrangements. Leukocyte markers and the corresponding antibodies and fluorochromes were selected based on their contribution in separating BCP-ALL cells from normal/regenerating BCP cells in multidimensional principal component analyses. After 5 multicenter design-test-evaluate-redesign phases with a total of 319 BCP-ALL patients at diagnosis, two 8-color antibody tubes were selected, which allowed separation between normal and malignant BCP cells in 99% of studied patients. These 2 tubes were tested with a new erythrocyte bulk-lysis protocol allowing acquisition of high cell numbers in 377 bone marrow follow-up samples of 178 BCP-ALL patients. Comparison with RQ-PCR-based MRD data showed a clear positive relation between the percentage concordant cases and the number of cells acquired. For those samples with >4 million cells acquired, concordant results were obtained in 93% of samples. Most discordances were clarified upon high-throughput sequencing of antigen-receptor rearrangements and blind multicenter reanalysis of flow cytometric data, resulting in an unprecedented concordance of 98% (97% for samples with MRD < 0.01%). In conclusion, the fully standardized EuroFlow BCP-ALL MRD strategy is applicable in >98% of patients with sensitivities at least similar to RQ-PCR (≤10-5), if sufficient cells (>4 × 106, preferably more) are evaluated.
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Kanderova V, Kuzilkova D, Stuchly J, Vaskova M, Brdicka T, Fiser K, Hrusak O, Lund-Johansen F, Kalina T. High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells. Mol Cell Proteomics 2016; 15:1246-61. [PMID: 26785729 DOI: 10.1074/mcp.m115.054593] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Indexed: 11/06/2022] Open
Abstract
Acute leukemia is a disease pathologically manifested at both genomic and proteomic levels. Molecular genetic technologies are currently widely used in clinical research. In contrast, sensitive and high-throughput proteomic techniques for performing protein analyses in patient samples are still lacking. Here, we used a technology based on size exclusion chromatography followed by immunoprecipitation of target proteins with an antibody bead array (Size Exclusion Chromatography-Microsphere-based Affinity Proteomics, SEC-MAP) to detect hundreds of proteins from a single sample. In addition, we developed semi-automatic bioinformatics tools to adapt this technology for high-content proteomic screening of pediatric acute leukemia patients.To confirm the utility of SEC-MAP in leukemia immunophenotyping, we tested 31 leukemia diagnostic markers in parallel by SEC-MAP and flow cytometry. We identified 28 antibodies suitable for both techniques. Eighteen of them provided excellent quantitative correlation between SEC-MAP and flow cytometry (p< 0.05). Next, SEC-MAP was applied to examine 57 diagnostic samples from patients with acute leukemia. In this assay, we used 632 different antibodies and detected 501 targets. Of those, 47 targets were differentially expressed between at least two of the three acute leukemia subgroups. The CD markers correlated with immunophenotypic categories as expected. From non-CD markers, we found DBN1, PAX5, or PTK2 overexpressed in B-cell precursor acute lymphoblastic leukemias, LAT, SH2D1A, or STAT5A overexpressed in T-cell acute lymphoblastic leukemias, and HCK, GLUD1, or SYK overexpressed in acute myeloid leukemias. In addition, OPAL1 overexpression corresponded to ETV6-RUNX1 chromosomal translocation.In summary, we demonstrated that SEC-MAP technology is a powerful tool for detecting hundreds of proteins in clinical samples obtained from pediatric acute leukemia patients. It provides information about protein size and reveals differences in protein expression between particular leukemia subgroups. Forty-seven of SEC-MAP identified targets were validated by other conventional method in this study.
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Affiliation(s)
- Veronika Kanderova
- From the ‡CLIP - Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2 Faculty of Medicine, Charles University in Prague, V Uvalu 84, 15006 Prague 5, Czech Republic
| | - Daniela Kuzilkova
- From the ‡CLIP - Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2 Faculty of Medicine, Charles University in Prague, V Uvalu 84, 15006 Prague 5, Czech Republic
| | - Jan Stuchly
- From the ‡CLIP - Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2 Faculty of Medicine, Charles University in Prague, V Uvalu 84, 15006 Prague 5, Czech Republic
| | - Martina Vaskova
- From the ‡CLIP - Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2 Faculty of Medicine, Charles University in Prague, V Uvalu 84, 15006 Prague 5, Czech Republic
| | - Tomas Brdicka
- §Institute of Molecular Genetics, Academy of Sciences of the Czech Republic; Videnska 1083, 14220 Prague, Czech Republic
| | - Karel Fiser
- From the ‡CLIP - Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2 Faculty of Medicine, Charles University in Prague, V Uvalu 84, 15006 Prague 5, Czech Republic
| | - Ondrej Hrusak
- From the ‡CLIP - Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2 Faculty of Medicine, Charles University in Prague, V Uvalu 84, 15006 Prague 5, Czech Republic
| | - Fridtjof Lund-Johansen
- ¶Department of Immunology, Oslo University Hospital, Rikshospitalet; Sognsvannsveien 20, 0372 Oslo, Norway
| | - Tomas Kalina
- From the ‡CLIP - Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2 Faculty of Medicine, Charles University in Prague, V Uvalu 84, 15006 Prague 5, Czech Republic;
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Lestanova Z, Bacova Z, Kiss A, Havranek T, Strbak V, Bakos J. Oxytocin Increases Neurite Length and Expression of Cytoskeletal Proteins Associated with Neuronal Growth. J Mol Neurosci 2015; 59:184-92. [DOI: 10.1007/s12031-015-0664-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 10/05/2015] [Indexed: 12/13/2022]
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Chen L, Luo Y, Liu T, Yuan Y, Gu H, Yang Y, Li L, Tan L. Label-free electrochemical immunoassay of Bcl-2 protein expression on tumor cells. Talanta 2015; 132:479-85. [DOI: 10.1016/j.talanta.2014.09.047] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 09/14/2014] [Accepted: 09/18/2014] [Indexed: 10/24/2022]
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Palmi C, Fazio G, Savino AM, Procter J, Howell L, Cazzaniga V, Vieri M, Longinotti G, Brunati I, Andrè V, Della Mina P, Villa A, Greaves M, Biondi A, D'Amico G, Ford A, Cazzaniga G. Cytoskeletal regulatory gene expression and migratory properties of B-cell progenitors are affected by the ETV6-RUNX1 rearrangement. Mol Cancer Res 2014; 12:1796-806. [PMID: 25061103 DOI: 10.1158/1541-7786.mcr-14-0056-t] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
UNLABELLED Although the ETV6-RUNX1 fusion is a frequent initiating event in childhood leukemia, its role in leukemogenesis is only partly understood. The main impact of the fusion itself is to generate and sustain a clone of clinically silent preleukemic B-cell progenitors (BCP). Additional oncogenic hits, occurring even several years later, are required for overt disease. The understanding of the features and interactions of ETV6-RUNX1-positive cells during this "latency" period may explain how these silent cells can persist and whether they could be prone to additional genetic changes. In this study, two in vitro murine models were used to investigate whether ETV6-RUNX1 alters the cellular adhesion and migration properties of BCP. ETV6-RUNX1-expressing cells showed a significant defect in the chemotactic response to CXCL12, caused by a block in CXCR4 signaling, as demonstrated by inhibition of CXCL12-associated calcium flux and lack of ERK phosphorylation. Moreover, the induction of ETV6-RUNX1 caused changes in the expression of cell-surface adhesion molecules. The expression of genes regulating the cytoskeleton was also affected, resulting in a block of CDC42 signaling. The abnormalities described here could alter the interaction of ETV6-RUNX1 preleukemic BCP with the microenvironment and contribute to the pathogenesis of the disease. IMPLICATIONS Alterations in the expression of cytoskeletal regulatory genes and migration properties of BCP represent early events in the evolution of the disease, from the preleukemic phase to the clinical onset, and suggest new strategies for effective eradication of leukemia.
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Affiliation(s)
- Chiara Palmi
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Grazia Fazio
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Angela M Savino
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Julia Procter
- Centre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom
| | - Louise Howell
- Haemato-Oncology Research Unit, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom
| | - Valeria Cazzaniga
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Margherita Vieri
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Giulia Longinotti
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Ilaria Brunati
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Valentina Andrè
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Pamela Della Mina
- Microscopy and Image Analysis Consortium, Università di Milano-Bicocca, Monza, Italy
| | - Antonello Villa
- Microscopy and Image Analysis Consortium, Università di Milano-Bicocca, Monza, Italy
| | - Mel Greaves
- Centre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom
| | - Andrea Biondi
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy.
| | - Giovanna D'Amico
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
| | - Anthony Ford
- Centre for Evolution and Cancer, Division of Molecular Pathology, The Institute of Cancer Research, Sutton, Surrey, United Kingdom
| | - Giovanni Cazzaniga
- Centro Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy
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Lin Q, Tan HT, Lim TK, Khoo A, Lim KH, Chung MCM. iTRAQ analysis of colorectal cancer cell lines suggests Drebrin (DBN1) is overexpressed during liver metastasis. Proteomics 2014; 14:1434-43. [PMID: 24610677 DOI: 10.1002/pmic.201300462] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 02/18/2014] [Accepted: 03/04/2014] [Indexed: 02/07/2023]
Affiliation(s)
- Qifeng Lin
- Department of Biochemistry; Yong Loo Lin School of Medicine; National University of Singapore; Singapore
| | - Hwee Tong Tan
- Department of Biochemistry; Yong Loo Lin School of Medicine; National University of Singapore; Singapore
| | - Teck Kwang Lim
- Department of Biological Sciences; Faculty of Science; National University of Singapore; Singapore
| | - Avery Khoo
- Department of Pathology; Singapore General Hospital; Singapore
| | - Kiat Hon Lim
- Department of Pathology; Singapore General Hospital; Singapore
| | - Maxey C. M. Chung
- Department of Biochemistry; Yong Loo Lin School of Medicine; National University of Singapore; Singapore
- Department of Biological Sciences; Faculty of Science; National University of Singapore; Singapore
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Abstract
Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite current advances in therapy consisting of surgery followed by chemotherapy and radiation, the overall survival rate still remains poor. Therapeutic failures are partly attributable to the highly infiltrative nature of tumor adjacent to normal brain parenchyma. Recently, evidence is mounting to suggest that actin cytoskeleton dynamics are critical components of the cell invasion process. Drebrin is an actin-binding protein involved in the regulation of actin filament organization, and plays a significant role in cell motility; however, the role of drebrin in glioma cell invasiveness has not yet been fully elucidated. Therefore, this study was aimed to clarify the role of drebrin in glioma cell morphology and cell motility. Here we show that drebrin is expressed in glioma cell lines and in operative specimens of GBM. We demonstrate that stable overexpression of drebrin in U87 cells leads to alterations in cell morphology, and induces increased invasiveness in vitro while knockdown of drebrin in U87 cells by small interfering RNA (siRNA) decreases invasion and migration. In addition, we show that depletion of drebrin by siRNA alters glioma cell morphology in A172 GBM cell line. Our results suggest that drebrin contributes to the maintenance of cell shape, and may play an important role in glioma cell motility.
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