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

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) catalyze...

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Published in:Human molecular genetics 2009-07, Vol.18 (14), p.2599-2608
Main Authors: Pinho, Salomé S., Reis, Celso A., Paredes, Joana, Magalhães, Ana Maria, Ferreira, António Carlos, Figueiredo, Joana, Xiaogang, Wen, Carneiro, Fátima, Gärtner, Fátima, Seruca, Raquel
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creator Pinho, Salomé S.
Reis, Celso A.
Paredes, Joana
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Figueiredo, Joana
Xiaogang, Wen
Carneiro, Fátima
Gärtner, Fátima
Seruca, Raquel
description 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 β1,6 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.
doi_str_mv 10.1093/hmg/ddp194
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subjects Biological and medical sciences
Cadherins - genetics
Cadherins - metabolism
Carcinoma - genetics
Carcinoma - metabolism
Cell Line, Tumor
Fundamental and applied biological sciences. Psychology
Gene Expression
Genetics of eukaryotes. Biological and molecular evolution
Glycosylation
Humans
Molecular and cellular biology
Molecular genetics
N-Acetylglucosaminyltransferases - genetics
N-Acetylglucosaminyltransferases - metabolism
Protein Processing, Post-Translational
Protein Transport
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Transcription. Transcription factor. Splicing. Rna processing
title The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin
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