Please use this identifier to cite or link to this item:
Author(s): Freitas, D
Campos, D
Gomes, J
Pinto, F
Macedo, JA
Matos, R
Mereiter, S
Pinto, MT
Polónia, A
Gärtner, F
Magalhães, A
Reis, CA
Title: O-glycans truncation modulates gastric cancer cell signaling and transcription leading to a more aggressive phenotype
Publisher: Elsevier
Issue Date: 2019
Abstract: 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.
Subject: Gastric cancer
Source: EBioMedicine, vol.40, p. 349-362
Related Information: info:eu-repo/grantAgreement/FCT/5876/147342/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

Files in This Item:
File Description SizeFormat 
10.1016-j.ebiom.2019.01.017.pdf5.4 MBAdobe PDFThumbnail

This item is licensed under a Creative Commons License Creative Commons