title: Loss and recovery of Mgat3 and GnT-III Mediated E-cadherin N-glycosylation is a mechanism involved in epithelial-mesenchymal-epithelial transitions.
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).
  
  
  RESULTS
  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
  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.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
authors.forename: Salomé S
authors.initials: SS
authors.lastname: Pinho
authors.forename: Patrícia
authors.initials: P
authors.lastname: Oliveira
authors.forename: Joana
authors.initials: J
authors.lastname: Cabral
authors.forename: Sandra
authors.initials: S
authors.lastname: Carvalho
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
authors.forename: Carla
authors.initials: C
authors.lastname: Oliveira
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D019295:Computational Biology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006031:Glycosylation; D047468:Immunoprecipitation; D051379:Mice; D008954:Models, Biological; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*
chemical_list: D015820:Cadherins; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase