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N‐ glycosylation by N ‐acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis
Author(s) -
Cui Jian,
Huang Wan,
Wu Bo,
Jin Jin,
Jing Lin,
Shi WenPu,
Liu ZhenYu,
Yuan Lin,
Luo Dan,
Li Ling,
Chen ZhiNan,
Jiang JianLi
Publication year - 2018
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5054
Subject(s) - basigin , metastasis , glycosylation , cancer research , pi3k/akt/mtor pathway , galectin , glycoprotein , epithelial–mesenchymal transition , glycan , integrin , biology , downregulation and upregulation , n linked glycosylation , microbiology and biotechnology , chemistry , cell , matrix metalloproteinase , signal transduction , cancer , biochemistry , gene , genetics
While the importance of protein N‐ glycosylation in cancer cell migration is well appreciated, the precise mechanisms by which N ‐acetylglucosaminyltransferase V (GnT‐V) regulates cancer processes remain largely unknown. In the current study, we report that GnT‐V‐mediated N‐ glycosylation of CD147/basigin, a tumor‐associated glycoprotein that carries β1,6‐ N ‐acetylglucosamine (β1,6‐GlcNAc) glycans, is upregulated during TGF‐β1‐induced epithelial‐to‐mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC). Interruption of β1,6‐GlcNAc glycan modification of CD147/basigin decreased matrix metalloproteinase (MMP) expression in HCC cell lines and affected the interaction of CD147/basigin with integrin β1. These results reveal that β1,6‐branched glycans modulate the biological function of CD147/basigin in HCC metastasis. Moreover, we showed that the PI3K/Akt pathway regulates GnT‐V expression and that inhibition of GnT‐V‐mediated N‐ glycosylation suppressed PI3K signaling. In summary, β1,6‐branched N‐ glycosylation affects the biological function of CD147/basigin and these findings provide a novel approach for the development of therapeutic strategies targeting metastasis. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.