N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin ß1 and promotes HCC metastasis.
J Pathol
; 245(1): 41-52, 2018 05.
Article
en En
| MEDLINE
| ID: mdl-29431199
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 ß1,6-N-acetylglucosamine (ß1,6-GlcNAc) glycans, is upregulated during TGF-ß1-induced epithelial-to-mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC). Interruption of ß1,6-GlcNAc glycan modification of CD147/basigin decreased matrix metalloproteinase (MMP) expression in HCC cell lines and affected the interaction of CD147/basigin with integrin ß1. These results reveal that ß1,6-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, ß1,6-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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glicosilación
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N-Acetilglucosaminiltransferasas
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Carcinoma Hepatocelular
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Basigina
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Factor de Crecimiento Transformador beta1
Límite:
Humans
Idioma:
En
Revista:
J Pathol
Año:
2018
Tipo del documento:
Article