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

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

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
JournalOncogene
Volume24
Issue number44
DOIs
Publication statusPublished - 2005 Oct 6

Fingerprint

Methyltransferases
Cadherins
DNA
Methylation
hepatitis B virus X protein
Neoplasms
CpG Islands
Cell Adhesion Molecules
Hepatitis B virus
Transcriptional Activation
Cell Movement
Hepatocellular Carcinoma
Suspensions
Carcinogenesis
Collagen
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Lee, Jung Ok ; Kwun, H. J. ; Jin, Kyu Jung ; Kyung, Hee Choi ; Do, Sik Min ; Jang, Kyung Lib. / Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1. In: Oncogene. 2005 ; Vol. 24, No. 44. pp. 6617-6625.
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Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1. / Lee, Jung Ok; Kwun, H. J.; Jin, Kyu Jung; Kyung, Hee Choi; Do, Sik Min; Jang, Kyung Lib.

In: Oncogene, Vol. 24, No. 44, 06.10.2005, p. 6617-6625.

Research output: Contribution to journalArticle

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