Loss and Recovery of Mgat3 and GnT-III Mediated E-cadherin N-glycosylation Is a Mechanism Involved in Epithelial-Mesenchymal-Epithelial Transitions

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Pinho, SS (Autor) Outra; Oliveira, P (Autor) Outra; Cabral, J (Autor) Outra; Carvalho, S (Autor) Outra; Huntsman, D (Autor) Outra; Gaerter, F (Autor) Outra; Seruca, R (Autor) FMUP; Celso Reis (Autor) ICBAS; Oliveira, C (Autor) Outra

Revista

Título: PLoS ONE

Vol. 7 Nº 4

Página Final: e33191

ISSN: 1932-6203

Editora: Public Library of Science

Indexação

ISI Web of Knowledge - 78 Citações

Scopus - 86 Citações

Outras Informações

ID Authenticus: P-002-C3R

DOI: 10.1371/journal.pone.0033191

Abstract (EN): Background: N-acetylglucosaminyltransferase-III (GnT-III) is a glycosyltransferase encoded by Mgat3 that catalyzes the addition of beta 1,4-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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9