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. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

• Authors: Jian Cui, Wan Huang, Bo Wu, Jin Jin, Lin Jing, Wen-Pu Shi, Zhen-Yu Liu, Lin Yuan, Dan Luo, Ling Li, Zhi-Nan Chen, Jian-Li Jiang
• Journal: The Journal of pathology (J Pathol) Vol. 245 Issue 1 Pg. 41-52 (05 2018) ISSN: 1096-9896 [Electronic] England
• PMID: 29431199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Chemical References

• BSG protein, human
• TGFB1 protein, human
• Transforming Growth Factor beta1
• Basigin
• N-Acetylglucosaminyltransferases
• alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase

Topics

• Basigin (drug effects)
• Carcinoma, Hepatocellular (metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Glycosylation (drug effects)
• Humans
• Liver Neoplasms (pathology)
• N-Acetylglucosaminyltransferases (pharmacology)
• Neoplasm Metastasis (pathology)
• Transforming Growth Factor beta1 (drug effects)