N-glycosylation by N-acetylglucosaminyltransferase IVa enhances the interaction of integrin ß1 with vimentin and promotes hepatocellular carcinoma cell motility.
Biochim Biophys Acta Mol Cell Res
; 1870(7): 119513, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37295747
ABSTRACT
N-glycosylation has been revealed to be tightly associated with cancer metastasis. As a key transferase that catalyzes the formation of ß1,4 N-acetylglucosamine (ß1,4GlcNAc) branches on the mannose core of N-glycans, N-acetylglucosaminyltransferase IVa (GnT-IVa) has been reported to be involved in hepatocellular carcinoma (HCC) metastasis by forming N-glycans; however, the underlying mechanisms are largely unknown. In the current study, we found that GnT-IVa was upregulated in HCC tissues and positively correlated with worse outcomes in HCC patients. We found that GnT-IVa could promote tumor growth in mice; notably, this effect was attenuated after mutating the enzymatic site (D445A) of GnT-IVa, suggesting that GnT-IVa regulated HCC progression by forming ß1,4GlcNAc branches. To mechanistically investigate the role of GnT-IVa in HCC, we conducted GSEA and GO functional analysis as well as in vitro experiments. The results showed that GnT-IVa could enhance HCC cell migration, invasion and adhesion ability and increase ß1,4GlcNAc branch glycans on integrin ß1 (ITGB1), a tumor-associated glycoprotein that is closely involved in cell motility by interacting with vimentin. Interruption of ß1,4GlcNAc branch glycan modification on ITGB1 could suppress the interaction of ITGB1 with vimentin and inhibit cell motility. These results revealed that GnT-IVa could promote HCC cell motility by affecting the biological functions of ITGB1 through N-glycosylation. In summary, our results revealed that GnT-IVa is highly expressed in HCC and can form ß1,4GlcNAc branches on ITGB1, which are essential for interactions with vimentin to promote HCC cell motility. These findings not only proposed a novel mechanism for GnT-IVa in HCC progression but also revealed the significance of N-glycosylation on ITGB1 during the process, which may provide a novel target for future HCC therapy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
N-Acetilglucosaminiltransferases
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China