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

• Type: Article in International Scientific Journal
• Date: 2009

Authors

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

Journal

Title: Human Molecular Genetics

Vol. 18 No. 14

Pages: 2599-2608

ISSN: 0964-6906

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 98 Citations

Scopus - 107 Citations

Pubmed / Medline

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10