Insulin/IGF-I Signaling Pathways Enhances Tumor Cell Invasion through Bisecting GlcNAc N-glycans Modulation. An Interplay with E-Cadherin

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Madureira de Freitas Junior, JCM (Autor) Outra; Carvalho, S (Autor) Outra; Dias, AM (Autor) Outra; Oliveira, P (Autor) Outra; Cabral, J (Autor) Outra; Seruca, R (Autor) FMUP; Oliveira, C (Autor) Outra; Morgado Diaz, JA (Autor) Outra; Celso Reis (Autor) ICBAS; Pinho, SS (Autor) Outra

Revista

Título: PLoS ONE

Vol. 8 Nº 1

Página Final: e81579

ISSN: 1932-6203

Editora: Public Library of Science

Indexação

ISI Web of Knowledge - 22 Citações

Scopus - 22 Citações

Outras Informações

ID Authenticus: P-006-JHW

DOI: 10.1371/journal.pone.0081579

Abstract (EN): Changes in glycosylation are considered a hallmark of cancer, and one of the key targets of glycosylation modifications is E-cadherin. We and others have previously demonstrated that E-cadherin has a role in the regulation of bisecting GlcNAc N-glycans expression, remaining to be determined the E-cadherin-dependent signaling pathway involved in this N-glycans expression regulation. In this study, we analysed the impact of E-cadherin expression in the activation profile of receptor tyrosine kinases such as insulin receptor (IR) and IGF-I receptor (IGF-IR). We demonstrated that exogenous E-cadherin expression inhibits IR, IGF-IR and ERK 1/2 phosphorylation. Stimulation with insulin and IGF-I in MDA-MD-435 cancer cells overexpressing E-cadherin induces a decrease of bisecting GlcNAc N-glycans that was accompanied with alterations on E-cadherin cellular localization. Concomitantly, IR/IGFIR signaling activation induced a mesenchymal-like phenotype of cancer cells together with an increased tumor cell invasion capability. Altogether, these results demonstrate an interplay between E-cadherin and IR/IGF-IR signaling as major networking players in the regulation of bisecting N-glycans expression, with important effects in the modulation of epithelial characteristics and tumor cell invasion. Here we provide new insights into the role that Insulin/IGF-I signaling play during cancer progression through glycosylation modifications.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 14