Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Carvalho, S (Autor) Outra; Catarino, TA (Autor) Outra; Dias, AM (Autor) Outra; Kato, M (Autor) Outra; Almeida, A (Autor) Outra; Hessling, B (Autor) Outra; Figueiredo, J (Autor) Outra; Gaertner, F (Autor) Outra; Sanches, JM (Autor) Outra; Ruppert, T (Autor) Outra; Miyoshi, E (Autor) Outra; Pierce, M (Autor) Outra; Carneiro F (Autor) FMUP; Kolarich, D (Autor) Outra; Seruca, R (Autor) Outra; Yamaguchi, Y (Autor) Outra; Taniguchi, N (Autor) Outra; Celso Reis (Autor) ICBAS; Pinho, SS (Autor) Outra

Revista

Título: Oncogene

Vol. 35

Páginas: 1619-1631

ISSN: 0950-9232

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 71 Citações

Scopus - 75 Citações

Outras Informações

ID Authenticus: P-00K-CCM

DOI: 10.1038/onc.2015.225

Abstract (EN): E-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 beta 1,6 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13