Please use this identifier to cite or link to this item: https://repositorio-aberto.up.pt/handle/10216/118210
Author(s): Carvalho, S
Oliveira, T
Bartels, M
Miyoshi, E
Pierce, M
Taniguchi, N
Carneiro, F
Seruca, R
Reis, CA
Strahl, S
Pinho, SS
Title: O-mannosylation and N-glycosylation: Two coordinated mechanisms regulating the tumour suppressor functions of E-cadherin in cancer
Publisher: Impact Journals
Issue Date: 2016
Abstract: Dysregulation of tumor suppressor protein E-cadherin is an early molecular event in cancer. O-mannosylation profile of E-cadherin is a newly-described posttranslational modification crucial for its adhesive functions in homeostasis. However, the role of O-mannosyl glycans in E-cadherin-mediated cell adhesion in cancer and their interplay with N-glycans remains largely unknown. We herein demonstrated that human gastric carcinomas exhibiting a non-functional E-cadherin display a reduced expression of O-mannosyl glycans concomitantly with increased modification with branched complex N-glycans. Accordingly, overexpression of MGAT5-mediated branched N-glycans both in gastric cancer cells and transgenic mice models led to a significant decrease of O-mannosyl glycans attached to E-cadherin that was associated with impairment of its tumour suppressive functions. Importantly, overexpression of protein O-mannosyltransferase 2 (POMT2) induced a reduced expression of branched N-glycans which led to a protective effect of E-cadherin biological functions. Overall, our results reveal a newly identified mechanism of (dys)regulation of E-cadherin that occur through the interplay between O-mannosylation and N-glycosylation pathway.
Subject: Adenocarcinoma/metabolism
Adenocarcinoma/pathology
Animals
Cadherins/metabolism
Glycosylation
Humans
Mannose/metabolism
Mice
Mice, Transgenic
Polysaccharides
Protein Processing, Post-Translational/physiology
Stomach Neoplasms/metabolism
Stomach Neoplasms/pathology
Tumor Suppressor Proteins/metabolism
URI: https://repositorio-aberto.up.pt/handle/10216/118210
Source: Oncotarget, vol.7(40), p. 65231-65246
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: Creative Commons Attribution 3.0 License
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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