Page 168 - D. Cancer biology

[D. Cancer biology-109]

Hepatitis B virus X protein enhances liver cancer cell

migration by regulating calmodulin-associated actin

polymerization

Inho Kang¹, Mi-jee Kim¹, Jeong Keun Ahn¹

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

University, Daejeon 305-764, Korea

Hepatocellular carcinoma (HCC) is one of the leading metastatic cancers with high mortality worldwide. Hepatitis B
virus is the main pathogen for various liver diseases including hepatocellular carcinoma. Among hepatitis B virus

(HBV) gene products, HBV X protein (HBx) is a multifunctional regulatory protein that plays pivotal roles in the
development of hepatitis, cirrhosis, and HCC caused by HBV infection.

By yeast two-hybrid assay, we identified that HBx physically interacts with calcium modulated protein, calmodulin
(CaM). In addition, HBx regulates the phosphorylation of cofilin through its interaction with CaM. As an actin

depolymerizing factor, cofilin is a key player in actin cytoskeleton dynamics to regulate cell migration. HBx elevates
the actin polymerization by suppressing CaM. CaM binds to HSP90 and inhibits LIMK which phosphorylates cofilin.

HBx interferes the interaction between CaM and HSP90, and subsequently elevates the phophorylated cofilin by
activating HSP90 and LIMK. HBx also promotes actin cytoskeletal rearrangement and liver cancer cell through

interacting with CaM.