title: Hepatitis C Virus E1 protein promotes cell migration and invasion by modulating cellular metastasis suppressor Nm23-H1.
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.
authors.affiliation: Department of Microbiology, University of Delhi, South Campus, New Delhi, India.
authors.forename: Lohit
authors.initials: L
authors.lastname: Khera
authors.affiliation: Department of Microbiology, University of Delhi, South Campus, New Delhi, India.
authors.forename: Catherine
authors.initials: C
authors.lastname: Paul
authors.affiliation: Department of Microbiology, University of Delhi, South Campus, New Delhi, India. Electronic address: rkaul@south.du.ac.in.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kaul
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D002465:Cell Movement; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C087035:E1 protein, Hepatitis C virus; D054778:NM23 Nucleoside Diphosphate Kinases; D014759:Viral Envelope Proteins; C517938:NME1 protein, human
keywords: Hepatitis C Virus; Hepatocellular carcinoma; Metastasis; Nm23-H1