title: Insulin/IGF-I signaling pathways enhances tumor cell invasion through bisecting GlcNAc N-glycans modulation. an interplay with E-cadherin.
abstract: 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/IGF-IR 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.
authors.affiliation: Division of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Julio Cesar Madureira
authors.initials: JC
authors.lastname: de-Freitas-Junior
authors.forename: Sandra
authors.initials: S
authors.lastname: Carvalho
authors.forename: Ana M
authors.initials: AM
authors.lastname: Dias
authors.forename: Patrícia
authors.initials: P
authors.lastname: Oliveira
authors.forename: Joana
authors.initials: J
authors.lastname: Cabral
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Carla
authors.initials: C
authors.lastname: Oliveira
authors.forename: José Andrés
authors.initials: JA
authors.lastname: Morgado-Díaz
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
authors.forename: Salomé S
authors.initials: SS
authors.lastname: Pinho
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006031:Glycosylation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011134:Polysaccharides / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D007328:Insulin; D011134:Polysaccharides; D051176:beta Catenin; D007334:Insulin-Like Growth Factor I; D000117:Acetylglucosamine