O-glycans truncation modulates gastric cancer cell signaling and transcription leading to a more aggressive phenotype

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Freitas, D (Author) Other; Campos, D (Author) Other; Gomes, J (Author) Other; Pinto, F (Author) Other; Macedo, JA (Author) Other; Matos, R (Author) Other; Mereiter, S (Author) Other; Pinto, MT (Author) Other; Polonia, A (Author) Other; Gartner, F (Author) Other; Magalhaes, A (Author) Other; Celso Reis (Author) ICBAS

Journal

Title: EBioMedicine

Vol. 40

Pages: 349-362

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 29 Citations

Scopus - 31 Citations

Other information

Authenticus ID: P-00Q-AMM

DOI: 10.1016/j.ebiom.2019.01.017

Abstract (EN): Background: Changes in glycosylation are known to play critical roles during gastric carcinogenesis. Expression of truncated O-glycans, such as the Sialyl-Tn (STn) antigen, is a common feature shared by many cancers and is associated with cancer aggressiveness and poor-prognosis. Methods: Glycoengineered cell lines were used to evaluate the impact of truncated O-glycans in cancer cell biology using in vitro functional assays, transcriptomic analysis and in vivo models. Tumor patients 'samples and datasets were used for clinical translational significance evaluation. Findings: In the present study, we demonstrated that gastric cancer cells expressing truncated O-glycans display major phenotypic alterations associated with higher cell motility and cell invasion. Noteworthy, the glycoengineered cancer cells overexpressing STn resulted in tumor xenografts with less cohesive features which had a critical impact on mice survival. Furthermore, truncation of O-glycans induced activation of EGFR and ErbB2 receptors and a transcriptomic signature switch of gastric cancer cells. The disclosed top activated genes were further validated in gastric tumors, revealing that SRPX2 and RUNX1 are concomitantly overexpressed in gastric carcinomas and its expression is associated with patients' poor-survival, highlighting their prognosis potential in clinical practice. Interpretation: This study discloses novel molecular links between O-glycans truncation frequently observed in cancer and key cellular regulators with major impact in tumor progression and patients' clinical outcome. (C) 2019 Published by Elsevier B.V.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14