Show simple item record

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.date.accessioned2017-06-13T00:12:11Z
dc.date.available2017-06-13T00:12:11Z
dc.date.issued2016
dc.identifier.issn0950-9232
dc.identifier.doi10.1038/onc.2015.225
dc.identifier.urihttp://hdl.handle.net/10072/339683
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.description.peerreviewedYes
dc.languageEnglish
dc.publisherNature Publishing Group
dc.relation.ispartofpagefrom1619
dc.relation.ispartofpageto1631
dc.relation.ispartofissue13
dc.relation.ispartofjournalOncogene
dc.relation.ispartofvolume35
dc.subject.fieldofresearchOncology and Carcinogenesis not elsewhere classified
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchcode111299
dc.subject.fieldofresearchcode1112
dc.subject.fieldofresearchcode1103
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


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record