O-mannosylation and N-glycosylation: two coordinated mechanisms regulating the tumour suppressor functions of E-cadherin in cancer

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Carvalho, S (Author) Other; Oliveira, T (Author) Other; Bartels, MF (Author) Other; Miyoshi, E (Author) Other; Pierce, M (Author) Other; Taniguchi, N (Author) Other; Carneiro F (Author) FMUP; Seruca, R (Author) Other; Celso Reis (Author) ICBAS; Strahl, S (Author) Other; Pinho, SS (Author) Other

Journal

Title: Oncotarget

Vol. 7

Pages: 65231-65246

ISSN: 1949-2553

Publisher: Impact Journals

Indexing

ISI Web of Knowledge - 33 Citations

Scopus - 35 Citations

Other information

Authenticus ID: P-00M-8K2

DOI: 10.18632/oncotarget.11245

Abstract (EN): Dysregulation of tumor suppressor protein E-cadherin is an early molecular event in cancer. O-mannosylation profile of E-cadherin is a newly-described post-ranslational 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16