The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin

• Tipo: Artigo em Revista Científica Internacional
• Data: 2009

Autores

Pinho, SS (Autor) Outra; Celso Reis (Autor) FEUP; Joana Paredes (Autor) FMUP; Magalhaes, AM (Autor) Outra; Ferreira, AC (Autor) Outra; Figueiredo, J (Autor) Outra; Wen, XG (Autor) Outra; Carneiro F (Autor) FMUP; Gaertner, F (Autor) Outra; Seruca, R (Autor) FMUP

Revista

Título: Human Molecular Genetics

Vol. 18 Nº 14

Páginas: 2599-2608

ISSN: 0964-6906

Editora: Oxford University Press

Indexação

ISI Web of Knowledge - 98 Citações

Scopus - 107 Citações

Pubmed / Medline

Outras Informações

ID Authenticus: P-003-HG9

DOI: 10.1093/hmg/ddp194

Abstract (EN): It has long been recognized that E-cadherin dysfunction is a major cause of epithelial cell invasion. However, very little is known about the post-transcriptional modifications of E-cadherin and its role in E-cadherin mediated tumor progression. N-acetylglucosaminyltransferase III (GnT-III) catalyzes the formation of a bisecting GlcNAc structure in N-glycans, and has been pointed as a metastasis suppressor. N-acetylglucosaminyltransferase V (GnT-V) catalyzes the addition of beta 1,6 GlcNAc branching of N-glycans, and has been associated to increase metastasis. The regulatory mechanism between E-cadherin expression and the remodeling of its oligosaccharides structures by GnT-III and GnT-V were explored in this study. We have demonstrated that wild-type E-cadherin regulates MGAT3 gene transcription resulting in increased GnT-III expression. We also showed that GnT-III and GnT-V competitively modified E-cadherin N-glycans. The GnT-III knockdown cells revealed a membrane de-localization of E-cadherin leading to its cytoplasmic accumulation. Further, the GnT-III knockdown cells also caused modifications of E-cadherin N-glycans catalyzed by GnT-III and GnT-V. Altogether our results have clarified the existence of a bidirectional crosstalk between E-cadherin and GnT-III/GnT-V that was, for the first time, reproduced in an in vivo model. This study opens new insights into the post-transcriptional modifications of E-cadherin in its biological function, in a tumor context.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10