Hepatitis B virus X protein specially regulates the sialyl lewis a synthesis among glycosylation events for metastasis = 암전이 당질화 과정에서 시알릴 루이스 a 합성을 조절하는 B형 간염바이러스의 X 단백질

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Title
Hepatitis B virus X protein specially regulates the sialyl lewis a synthesis among glycosylation events for metastasis = 암전이 당질화 과정에서 시알릴 루이스 a 합성을 조절하는 B형 간염바이러스의 X 단백질
Author(s)
T W Chung; S J Kim; H J Choi; K H Song; U H Jin; Dae Yeul Yu; J K Seong; J G Kim; K J Kim; Jeong Heon Ko; K T Ha; Y C Lee; C H Kim
Bibliographic Citation
Molecular Cancer, vol. 13, no. 1, pp. 222-222
Publication Year
2014
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.
Keyword
E-selectinEndothelial cellsHepatitis B virusHepatocellular carcinomaSialyl lewis antigen
ISSN
1476-4598
Publisher
Springer-BMC
DOI
http://dx.doi.org/10.1186/1476-4598-13-222
Type
Article
Appears in Collections:
Synthetic Biology and Bioengineering Research Institute > Genome Editing Research Center > 1. Journal Articles
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