Abstract
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.
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