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dc.contributor.authorCarvalho, S
dc.contributor.authorCatarino, TA
dc.contributor.authorDias, AM
dc.contributor.authorKato, M
dc.contributor.authorAlmeida, A
dc.contributor.authorHessling, B
dc.contributor.authorFigueiredo, J
dc.contributor.authorGaertner, F
dc.contributor.authorSanches, JM
dc.contributor.authorRuppert, T
dc.contributor.authorMiyoshi, E
dc.contributor.authorPierce, M
dc.contributor.authorCarneiro, F
dc.contributor.authorKolarich, D
dc.contributor.authorSeruca, R
dc.contributor.authorYamaguchi, Y
dc.contributor.authorTaniguchi, N
dc.contributor.authorReis, CA
dc.contributor.authorPinho, SS
dc.description.abstractE-cadherin is a central molecule in the process of gastric carcinogenesis and its posttranslational modifications by N-glycosylation have been described to induce a deleterious effect on cell adhesion associated with tumor cell invasion. However, the role that site-specific glycosylation of E-cadherin has in its defective function in gastric cancer cells needs to be determined. Using transgenic mice models and human clinical samples, we demonstrated that N-acetylglucosaminyltransferase V (GnT-V)-mediated glycosylation causes an abnormal pattern of E-cadherin expression in the gastric mucosa. In vitro models further indicated that, among the four potential N-glycosylation sites of E-cadherin, Asn-554 is the key site that is selectively modified with β1,6 GlcNAc-branched N-glycans catalyzed by GnT-V. This aberrant glycan modification on this specific asparagine site of E-cadherin was demonstrated to affect its critical functions in gastric cancer cells by affecting E-cadherin cellular localization, cis-dimer formation, molecular assembly and stability of the adherens junctions and cell–cell aggregation, which was further observed in human gastric carcinomas. Interestingly, manipulating this site-specific glycosylation, by preventing Asn-554 from receiving the deleterious branched structures, either by a mutation or by silencing GnT-V, resulted in a protective effect on E-cadherin, precluding its functional dysregulation and contributing to tumor suppression.
dc.publisherNature Publishing Group
dc.subject.fieldofresearchOncology and Carcinogenesis not elsewhere classified
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.titlePreventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorKolarich, Daniel

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