Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes
| العنوان: | Arf6-driven endocytic recycling of CD147 determines HCC malignant phenotypes |
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| المؤلفون: | Linjia Su, Zhe Ma, Chuan-Shan Zhang, Gui-qiu Liu, Jing Li, Sihe Zhang, Guhe Jia, Yongjun Piao, Shanshan Qi, Qing Zhang |
| المصدر: | Journal of Experimental & Clinical Cancer Research, Vol 38, Iss 1, Pp 1-17 (2019) Journal of Experimental & Clinical Cancer Research : CR |
| بيانات النشر: | BMC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Carcinoma, Hepatocellular, Endocytic recycling, RAC1, lcsh:RC254-282, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, medicine, Cell Adhesion, Humans, Arf6, Cell adhesion, Cell Aggregation, rab5 GTP-Binding Proteins, medicine.diagnostic_test, Chemistry, Cell adhesion molecule, ADP-Ribosylation Factors, Research, Liver Neoplasms, Malignant phenotype, Cancer, Hep G2 Cells, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Immunohistochemistry, Cell aggregation, Endocytosis, Up-Regulation, 030104 developmental biology, Phenotype, Oncology, ADP-Ribosylation Factor 6, rab GTP-Binding Proteins, 030220 oncology & carcinogenesis, Cancer research, Basigin, CD147, Liver cancer |
| الوصف: | BackgroundAdhesion molecules distributed on the cell-surface depends upon their dynamic trafficking that plays an important role during cancer progression. ADP-ribosylation factor 6 (Arf6) is a master regulator of membrane trafficking. CD147, a tumor-related adhesive protein, can promote the invasion of liver cancer. However, the role of Arf6 in CD147 trafficking and its contribution to liver cancer progression remain unclear.MethodsStable liver cancer cell lines with Arf6 silencing and over-expression were established. Confocal imaging, flow cytometry, biotinylation and endomembrane isolation were used to detect CD147 uptake and recycling. GST-pull down, gelatin zymography, immunofluorescence, cell adhesion, aggregation and tight junction formation, Transwell migration, and invasion assays were used to examine the cellular phenotypes. GEPIA bioinformatics, patient’s specimens and electronic records collection, and immunohistochemistry were performed to obtain the clinical relevance for Arf6-CD147 signaling.ResultsWe found that the endocytic recycling of CD147 in liver cancer cells was controlled by Arf6 through concurrent Rab5 and Rab22 activation. Disruption of Arf6-mediated CD147 trafficking reduced the cell-matrix and cell-cell adhesion, weakened cell aggregation and junction stability, attenuated MMPs secretion and cytoskeleton reorganization, impaired HGF-stimulated Rac1 activation, and markedly decreased the migration and invasion of liver cancer cells. Moreover, high-expression of the Arf6-CD147 signaling components in HCC (hepatocellular carcinoma) was closely correlated with poor clinical outcome of patients.ConclusionsOur results revealed that Arf6-mediated CD147 endocytic recycling is required for the malignant phenotypes of liver cancer. The Arf6-driven signaling machinery provides excellent biomarkers or therapeutic targets for the prevention of liver cancer. |
| اللغة: | English |
| تدمد: | 1756-9966 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::338e67f7fbc34f8f0fdeffadb996bcde http://link.springer.com/article/10.1186/s13046-019-1464-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....338e67f7fbc34f8f0fdeffadb996bcde |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17569966 |
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