N-glycosylation by N-acetylglucosaminyltransferase V Enhances the Interaction of CD147/Basigin with Integrin β1 and Promotes HCC Metastasis

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.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2EVMpUo