Hepatitis C Virus E1 protein promotes cell migration and invasion by modulating cellular metastasis suppressor Nm23-H1

Virology. 2017 Jun:506:110-120. doi: 10.1016/j.virol.2017.03.014. Epub 2017 Apr 2.

Abstract

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and its incidence is on the rise largely attributed to Hepatitis C virus (HCV) related liver cancer. A distinct feature of HCV associated HCC is the substantially increased incidence of metastasis compared to non-viral or HBV associated HCC. Nm23-H1 is the first reported human metastasis suppressor down-regulated in many human metastatic cancers. Nm23-H1 functions are modulated in several virus associated cancers. Our study now shows that HCV E1 protein expression as well as HCV infection induces pro-metastatic effect on cancer cells which is simultaneous to Nm23-H1 transcriptional down-regulation and Nm23-H1 protein degradation. Moreover, Nm23-H1 intracellular localization is significantly altered in cells expressing HCV E1 protein. Importantly, overexpression of Nm23-H1 can rescue the cancer cells from pro-metastatic effects of HCV E1 and HCV infection. Our limited study provides evidence for role for Nm23-H1 in HCV mediated cancer metastasis.

Keywords: Hepatitis C Virus; Hepatocellular carcinoma; Metastasis; Nm23-H1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / physiopathology*
  • Carcinoma, Hepatocellular / virology
  • Cell Movement
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Hepacivirus / genetics
  • Hepacivirus / metabolism*
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / physiopathology*
  • Liver Neoplasms / virology
  • NM23 Nucleoside Diphosphate Kinases / genetics
  • NM23 Nucleoside Diphosphate Kinases / metabolism*
  • Neoplasm Invasiveness
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*

Substances

  • E1 protein, Hepatitis C virus
  • NM23 Nucleoside Diphosphate Kinases
  • Viral Envelope Proteins
  • NME1 protein, human