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

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 El protein expression as well as HCV infection induces pro-metastatic effect on cancer cells which is simultaneous to Nm23-Hl transcriptional down-regulation and Nm23-H1 protein degradation. Moreover, Nm23-H1 intracellular localization is significantly altered in cells expressing HCV El protein. Importantly, overexpression of Nm23-H1 can rescue the cancer cells from pro-metastatic effects of HCV El and HCV infection. Our limited study provides evidence for role for Nm23-H1 in HCV mediated cancer metastasis.