Loss and recovery of Mgat3 and GnT-III mediated E-cadherin N-glycosylation is a mechanism involved in epithelial-Mesenchymal-Epithelial transitions

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Abstract

Background: N-acetylglucosaminyltransferase-III (GnT-III) is a glycosyltransferase encoded by Mgat3 that catalyzes the addition of β1,4-bisecting-N-acetylglucosamine on N-glycans. GnT-III has been pointed as a metastases suppressor having varying effects on cell adhesion and migration. We have previously described the existence of a functional feedback loop between E-cadherin expression and GnT-III-mediated glycosylation. The effects of GnT-III-mediated glycosylation on E-cadherin expression and cellular phenotype lead us to evaluate Mgat3 and GnT-III-glycosylation role during Epithelial-Mesenchymal-Transition (EMT) and the reverted process, Mesenchymal-Epithelial-Transition (MET). Methodology/Principal Findings: We analyzed the expression profile and genetic mechanism controlling Mgat3 expression as well as GnT-III-mediated glycosylation, in general and specifically on E-cadherin, during EMT/MET. We found that during EMT, Mgat3 expression was dramatically decreased and later recovered when cells returned to an epithelial-like phenotype. We further identified that Mgat3 promoter methylation/demethylation is involved in this expression regulation. The impact of Mgat3 expression variation, along EMT/MET, leads to a variation in the expression levels of the enzymatic product of GnT-III (bisecting GlcNAc structures), and more importantly, to the specific modification of E-cadherin glycosylation with bisecting GlcNAc structures. Conclusions/Significance: Altogether, this work identifies for the first time Mgat3 glycogene expression and GnT-III-mediated glycosylation, specifically on E-cadherin, as a novel and major component of the EMT/MET mechanism signature, supporting its role during EMT/MET. © 2012 Pinho et al.

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Pinho, S. S., Oliveira, P., Cabral, J., Carvalho, S., Huntsman, D., Gärtner, F., … Oliveira, C. (2012). Loss and recovery of Mgat3 and GnT-III mediated E-cadherin N-glycosylation is a mechanism involved in epithelial-Mesenchymal-Epithelial transitions. PLoS ONE, 7(3). https://doi.org/10.1371/journal.pone.0033191

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