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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 |
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creator | Pinho, Salomé S. Reis, Celso A. Paredes, Joana Magalhães, Ana Maria Ferreira, António Carlos 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. |
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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.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddp194</identifier><identifier>PMID: 19403558</identifier><identifier>CODEN: HNGEE5</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>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</subject><ispartof>Human molecular genetics, 2009-07, Vol.18 (14), p.2599-2608</ispartof><rights>The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org 2009</rights><rights>2009 INIST-CNRS</rights><rights>The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c543t-be62aa2d43943af1d164efca6654df9af4bf18de659c51b8f32b41df754c18a13</citedby><cites>FETCH-LOGICAL-c543t-be62aa2d43943af1d164efca6654df9af4bf18de659c51b8f32b41df754c18a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21640271$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19403558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pinho, Salomé S.</creatorcontrib><creatorcontrib>Reis, Celso A.</creatorcontrib><creatorcontrib>Paredes, Joana</creatorcontrib><creatorcontrib>Magalhães, Ana Maria</creatorcontrib><creatorcontrib>Ferreira, António Carlos</creatorcontrib><creatorcontrib>Figueiredo, Joana</creatorcontrib><creatorcontrib>Xiaogang, Wen</creatorcontrib><creatorcontrib>Carneiro, Fátima</creatorcontrib><creatorcontrib>Gärtner, Fátima</creatorcontrib><creatorcontrib>Seruca, Raquel</creatorcontrib><title>The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><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.</description><subject>Biological and medical sciences</subject><subject>Cadherins - genetics</subject><subject>Cadherins - metabolism</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Glycosylation</subject><subject>Humans</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>N-Acetylglucosaminyltransferases - genetics</subject><subject>N-Acetylglucosaminyltransferases - metabolism</subject><subject>Protein Processing, Post-Translational</subject><subject>Protein Transport</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Transcription. Transcription factor. Splicing. 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Psychology</topic><topic>Gene Expression</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Glycosylation</topic><topic>Humans</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>N-Acetylglucosaminyltransferases - genetics</topic><topic>N-Acetylglucosaminyltransferases - metabolism</topic><topic>Protein Processing, Post-Translational</topic><topic>Protein Transport</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Transcription. Transcription factor. Splicing. Rna processing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pinho, Salomé S.</creatorcontrib><creatorcontrib>Reis, Celso A.</creatorcontrib><creatorcontrib>Paredes, Joana</creatorcontrib><creatorcontrib>Magalhães, Ana Maria</creatorcontrib><creatorcontrib>Ferreira, António Carlos</creatorcontrib><creatorcontrib>Figueiredo, Joana</creatorcontrib><creatorcontrib>Xiaogang, Wen</creatorcontrib><creatorcontrib>Carneiro, Fátima</creatorcontrib><creatorcontrib>Gärtner, Fátima</creatorcontrib><creatorcontrib>Seruca, Raquel</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pinho, Salomé S.</au><au>Reis, Celso A.</au><au>Paredes, Joana</au><au>Magalhães, Ana Maria</au><au>Ferreira, António Carlos</au><au>Figueiredo, Joana</au><au>Xiaogang, Wen</au><au>Carneiro, Fátima</au><au>Gärtner, Fátima</au><au>Seruca, Raquel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2009-07-15</date><risdate>2009</risdate><volume>18</volume><issue>14</issue><spage>2599</spage><epage>2608</epage><pages>2599-2608</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><coden>HNGEE5</coden><abstract>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.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>19403558</pmid><doi>10.1093/hmg/ddp194</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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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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