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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Hepatitis B virus X protein enhances liver cancer cell migration by regulating calmodulin-associated actin polymerization

  • Kim, Mi-jee (Department of Microbiology & Molecular Biology, College of Biological Science and Biotechnology, Chungnam National University) ;
  • Kim, Jinchul (Department of Microbiology & Molecular Biology, College of Biological Science and Biotechnology, Chungnam National University) ;
  • Im, Jin-su (Department of Microbiology & Molecular Biology, College of Biological Science and Biotechnology, Chungnam National University) ;
  • Kang, Inho (Department of Microbiology & Molecular Biology, College of Biological Science and Biotechnology, Chungnam National University) ;
  • Ahn, Jeong Keun (Department of Microbiology & Molecular Biology, College of Biological Science and Biotechnology, Chungnam National University)
  • Received : 2021.06.30
  • Accepted : 2021.08.06
  • Published : 2021.12.31
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Abstract

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), which is a highly aggressive cancer. HBV X protein (HBx), one of four HBV gene products, plays pivotal roles in the development and metastasis of HCC. It has been reported that HBx induces liver cancer cell migration and reorganizes actin cytoskeleton, however the molecular basis for actin cytoskeleton reorganization remains obscure. In this study, we for the first time report that HBx promotes actin polymerization and liver cancer cell migration by regulating calcium modulated protein, calmodulin (CaM). HBx physically interacts with CaM to control the level of phosphorylated cofilin, an actin depolymerizing factor. Mechanistically, HBx interacts with CaM, liberates Hsp90 from its inhibitory partner CaM, and increases the activity of Hsp90, thus activating LIMK1/cofilin pathway. Interestingly, the interaction between HBx and CaM is calcium-dependent and requires the CaM binding motif on HBx. These results indicate that HBx modulates CaM which plays a regulatory role in Hsp90/LIMK1/cofilin pathway of actin reorganization, suggesting a new mechanism of HBV-induced HCC metastasis specifically derived by HBx.

Keywords

Acknowledgement

This work was supported by the research fund of Chungnam National University.

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