Hepatitis C Virus Enhances the Invasiveness of Hepatocellular Carcinoma via EGFR-Mediated Invadopodia Formation and Activation

Autor: 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
Jazyk: angličtina
Rok vydání: 2019
Předmět:
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
Zdroj: Cells
Volume 8
Issue 11
Cells, Vol 8, Iss 11, p 1395 (2019)
ISSN: 2073-4409
DOI: 10.3390/cells8111395
Popis: 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.
Databáze: OpenAIRE
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