Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1

Jung Ok Lee, H. J. Kwun, Kyu Jung Jin, Hee Choi Kyung, Sik Min Do, Kyung Lib Jang

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171 Citations (Scopus)


E-cadherin is a key cell adhesion molecule implicated as a tumor suppressor, which is frequently altered in hepatocellular carcinoma, especially in hepatitis B virus (HBV)-related tumors. Here, we report that HBV X protein (HBx) represses E-cadherin expression at the transcription level. Based on the differential effects of HBx natural variants, we determined that Lys-130 in the transactivation domain of HBx is critical for the E-cadherin repression. The repression effect of HBx was abolished after treatment with DNA methyltransferase inhibitor, 5′-Aza-2′dC. In addition, methylation-specific PCR analysis revealed that the CpG island 1 of E-cadherin promoter is hypermethylated by HBx. Furthermore, HBx induces DNA methyltransferase 1 expression by stimulating its transcription. Therefore, we conclude that HBx represses E-cadherin expression by inducing methylation-mediated promoter inactivation. The reduced E-cadherin expression results in dramatic morphological changes of the HBx-expressing cells. In addition, HBx-expressing cells aggregate poorly in suspension culture, reflecting their altered intercellular interactions. The biological significance was further demonstrated by the increased collagen invasion ability of HBx-expressing cells. Therefore, the present study suggests that HBx plays a role during hepatocellular carcinogenesis by favoring cell detachment from the surrounding cells and migration outside of the primary tumor site.

Original languageEnglish
Pages (from-to)6617-6625
Number of pages9
Issue number44
Publication statusPublished - 2005 Oct 6

Bibliographical note

Funding Information:
This work was supported by a grant from Pusan National University. HJK was supported by a postdoctoral training fellowship from Pusan National University.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research


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