title: Hepatitis B virus X protein specially regulates the sialyl lewis a synthesis among glycosylation events for metastasis.
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.
  
  
  CONCLUSIONS
  HBx targets the specific glycosyltransferases for the SLA synthesis and this process regulates hematogenous cancer cell adhesion to endothelial cells for cancer metastasis.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chung
authors.forename: Seok-Jo
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Kwon-Ho
authors.initials: KH
authors.lastname: Song
authors.forename: Un-Ho
authors.initials: UH
authors.lastname: Jin
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
authors.forename: Je-Kyung
authors.initials: JK
authors.lastname: Seong
authors.forename: Jong-Guk
authors.initials: JG
authors.lastname: Kim
authors.forename: Keuk-Jun
authors.initials: KJ
authors.lastname: Kim
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Ko
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.forename: Young-Choon
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Molecular and Cellular Glycobiology Laboratory, Department of Biological Science, SungKyunKwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon, Kyunggi-Do 440-746, South Korea. chkimbio@skku.edu.
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000818:Animals; D018395:CA-19-9 Antigen; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016256:Lewis X Antigen / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009844:Oligosaccharides / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D018395:CA-19-9 Antigen; D016256:Lewis X Antigen; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D016695:Glycosyltransferases