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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

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

Journal

Title: PLoS ONE

Vol. 8 No. 1

Final page: e81579

ISSN: 1932-6203

Publisher: Public Library of Science

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 22 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14