Hepatitis B virus X protein specially regulates the sialyl lewis a synthesis among glycosylation events for metastasis

Tae Wook Chung, Seok Jo Kim, Hee Jung Choi, Kwon Ho Song, Un Ho Jin, Dae Yeul Yu, Je Kyung Seong, Jong Guk Kim, Keuk Jun Kim, Jeong Heon Ko, Ki Tae Ha, Young Choon Lee, Cheorl Ho Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: The metastasis of hematogenous cancer cells is associated with abnormal glycosylation such as sialyl lewis antigens. Although the hepatitis B virus X protein (HBx) plays important role in liver disease, the precise function of HBx on aberrant glycosylation for metastasis remains unclear.Methods: The human hepatocellular carcinoma tissues, HBx transgenic mice and HBx-transfected cells were used to check the correlation of expressions between HBx and Sialyl lewis antigen for cancer metastasis. To investigate whether expression levels of glycosyltransferases induced in HBx-transfected cells are specifically associated with sialyl lewis A (SLA) synthesis, which enhances metastasis by interaction of liver cancer cells with endothelial cells, ShRNA and siRNAs targeting specific glycosyltransferases were used.Results: HBx expression in liver cancer region of HCC is associated with the specific synthesis of SLA. Furthermore, the SLA was specifically induced both in liver tissues from HBx-transgenic mice and in in vitro HBx-transfected cells. HBx increased transcription levels and activities of α2-3 sialyltransferases (ST3Gal III), α1-3/4 fucosyltransferases III and VII (FUT III and VII) genes, which were specific for SLA synthesis, allowing dramatic cell-cell adhesion for metastatic potential. Interestingly, HBx specifically induced expression of N-acetylglucosamine-β1-3 galactosyltransferase V (β1-3GalT 5) gene associated with the initial synthesis of sialyl lewis A, but not β1-4GalT I. The β1-3GalT 5 shRNA suppressed SLA expression by HBx, blocking the adhesion of HBx-transfected cells to the endothelial cells. Moreover, β1-3GalT 5 silencing suppressed lung metastasis of HBx-transfected cells in in vivo lung metastasis system.Conclusion: HBx targets the specific glycosyltransferases for the SLA synthesis and this process regulates hematogenous cancer cell adhesion to endothelial cells for cancer metastasis.

Original languageEnglish (US)
Article number222
JournalMolecular Cancer
Volume13
Issue number1
DOIs
StatePublished - Sep 25 2014

Keywords

  • E-selectin
  • Endothelial cells
  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Sialyl lewis antigen

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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