A dual role for hypoxia inducible factor-1α in the hepatitis C virus lifecycle and hepatoma migration

• DOI: 10.1016/j.jhep.2011.11.018
• Publication Date: 2011-12-16T10:29:02Z
• Authors: Garrick K. Wilson; Claire L. Brimacombe; Ian A. Rowe; Gary M. Reynolds; Nicola F. Fletcher; Zania Stamataki; Ricky H. Bhogal; Maria L. Simões; Margaret Ashcroft; Simon C. Afford; Ragai R. Mitry; Anil Dhawan; Christopher J. Mee; Stefan G. Hübscher; Peter Balfe; Jane A. McKeating
• Keywords: Adherens junction

Hepatitis C virus (HCV) causes progressive liver disease and is a major risk factor for the development of hepatocellular carcinoma (HCC). However, role infection in HCC pathogenesis poorly understood. We investigated effect(s) HCV viral glycoprotein expression on hepatoma biology to gain insights into associated HCC.We assessed polarity, migration invasion.HCV glycoproteins perturb tight adherens junction protein expression, increase epithelial mesenchymal transition markers Snail Twist via stabilizing hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates many genes involved tumor growth metastasis, including vascular endothelial (VEGF) transforming factor-beta (TGF-β). Neutralization both factors shows different roles VEGF TGFβ regulating polarity migration, respectively. Importantly, we confirmed these observations infected primary human hepatocytes. Inhibition reversed permeability significantly reduced replication, demonstrating dual cellular processes that are deregulated cancers life cycle.These data provide new cancer-promoting effects offer approaches treatment.