Hepatitis C Virus Enhances the Invasiveness of Hepatocellular Carcinoma via EGFR-Mediated Invadopodia Formation and Activation
| العنوان: | Hepatitis C Virus Enhances the Invasiveness of Hepatocellular Carcinoma via EGFR-Mediated Invadopodia Formation and Activation |
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| المؤلفون: | Alessandro Genna, Liat Ninio, Kolluru D. Srikanth, Meital Gal-Tanamy, Roba Dabour, Tom Domovitz, Abraham Nissani, Shams Twafra, Hava Gil-Henn, Ateret Davidovich, Erez Avraham, Tomer Meirson |
| المصدر: | Cells Volume 8 Issue 11 Cells, Vol 8, Iss 11, p 1395 (2019) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, hepatitis C virus, Carcinoma, Hepatocellular, Hepatitis C virus, Gene Expression, Hepacivirus, Mice, SCID, medicine.disease_cause, Article, Metastasis, Mice, 03 medical and health sciences, hepatocellular carcinoma (HCC), 0302 clinical medicine, Mice, Inbred NOD, Cell Line, Tumor, medicine, Animals, Humans, metastasis, Neoplasm Invasiveness, Epidermal growth factor receptor, lcsh:QH301-705.5, Protein Tyrosine Phosphatase, Non-Receptor Type 2, biology, business.industry, Liver Neoplasms, Cancer, General Medicine, Gene signature, Prognosis, medicine.disease, invasion, Hepatitis C, digestive system diseases, ErbB Receptors, 030104 developmental biology, lcsh:Biology (General), 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Podosomes, Invadopodia, Cancer research, biology.protein, business, Tyrosine kinase, Signal Transduction |
| الوصف: | Hepatocellular carcinoma (HCC) represents the fifth most common cancer worldwide and the third cause of cancer-related mortality. Hepatitis C virus (HCV) is the leading cause of chronic hepatitis, which often results in liver fibrosis, cirrhosis, and eventually HCC. HCV is the most common risk factor for HCC in western countries and leads to a more aggressive and invasive disease with poorer patient survival rates. However, the mechanism by which the virus induces the metastatic spread of HCC tumor cells through the regulation of invadopodia, the key features of invasive cancer, is still unknown. Here, the integration of transcriptome with functional kinome screen revealed that HCV infection induced invasion and invadopodia-related gene expression combined with activation of host cell tyrosine kinases, leading to invadopodia formation and maturation and consequent cell invasiveness in vitro and in vivo. The promotion of invadopodia following HCV infection was mediated by the sustained stimulation of epidermal growth factor receptor (EGFR) via the viral NS3/4A protease that inactivates the T-cell protein tyrosine phosphatase (TC-PTP), which inhibits EGFR signaling. Characterization of an invadopodia-associated gene signature in HCV-mediated HCC tumors correlated with the invasiveness of HCC and poor patient prognosis. These findings might lead to new prognostic and therapeutic strategies for virus-mediated invasive cancer. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| DOI: | 10.3390/cells8111395 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d18db74f7f238f80fddf39e7cf0e912 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3d18db74f7f238f80fddf39e7cf0e912 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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| DOI: | 10.3390/cells8111395 |