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Biochim Biophys Acta. 1999 Dec 6;1473(1):21-34.

Glycoprotein glycosylation and cancer progression.

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1
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Rm. 876, M5G 1X5, Toronto, Ont., Canada. dennis@mshri.on.ca

Abstract

Glycosylation of glycoproteins and glycolipids is one of many molecular changes that accompany malignant transformation. GlcNAc-branched N-glycans and terminal Lewis antigen sequences have been observed to increase in some cancers, and to correlate with poor prognosis. Herein, we review evidence that beta1, 6GlcNAc-branching of N-glycans contributes directly to cancer progression, and we consider possible functions for the glycans. Mgat5 encodes N-acetylglucosaminyltransferase V (GlcNAc-TV), the Golgi enzyme required in the biosynthesis of beta1,6GlcNAc-branched N-glycans. Mgat5 expression is regulated by RAS-RAF-MAPK, a signaling pathway commonly activated in tumor cells. Ectopic expression of GlcNAc-TV in epithelial cells results in morphological transformation and tumor growth in mice, and over expression in carcinoma cells has been shown to induce metastatic spread. Ectopic expression of GlcNAc-TIII, an enzyme that competes with GlcNAc-TV for acceptor, suppresses metastasis in B16 melanoma cells. Furthermore, breast cancer progression and metastasis induced by a viral oncogene expressed in transgenic mice is markedly suppressed in a GlcNAc-TV-deficient background. Mgat5 gene expression and beta1, 6GlcNAc-branching of N-glycans are associated with cell motility, a required phenotype of malignant cells.

PMID:
10580127
[Indexed for MEDLINE]
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