Page 104 - D. Cancer biology

[D. Cancer biology-67]

Hepatitis B virus X protein promotes hepatocellular carcinogenesis

and metastasis through regulating VHL binding protein1

Inho Kang¹, Ji Ae Kim¹, Sung-min Kang¹, Hanwoon Park¹, Jeong Keun Ahn¹˙*

¹Department of Microbiology & Molecular Biology, College of Bioscience and Biotechnology, Chungnam National

University, Daejeon 305-764, KOREA

Chronic hepatitis B virus (HBV) infection is a leading cause of various liver diseases including hepatocellular
carcinoma. Among HBV proteins, hepatitis X protein (HBx) plays critical roles in the development of hepatocellular

carcinoma. However the precise mechanism of HBx involved in HCC formation is still unclear. In this study, we

demonstrated that HBx binds to VHL binding protein 1 (VBP1), and subsequently interrupts the interaction between
VBP1 and Von Hippel-Lindau protein (pVHL) which enhances HIF-1α degradation. We also revealed that HBx
interrupts pVHL stabilization induced by VBP1, and consequently stabilizes HIF-1α. It has been reported that

upregulated HIF-1α promotes the tumor formation and enhances the epithelial-mesenchymal transition. Taken
together, this study suggest a new mechanism of HBx which has vital roles in liver carcinogenesis and metastasis.