Integrin beta 1 orchestrates the abnormal cell-matrix attachment and invasive behaviour of E-cadherin dysfunctional cells

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Figueiredo, J (Author) Other; Ferreira, RM (Author) Other; Xu, H (Author) Other; Goncalves, M (Author) Other; Barros Carvalho, A (Author) Other; Cravo, J (Author) Other; Maia, AF (Author) Other; Carneiro, P (Author) Other; Figueiredo C (Author) FMUP; Smith, ML (Author) Other; Stamenovic, D (Author) Other; Morais de Sa, E (Author) Other; Seruca, R (Author) Other

Journal

Title: Gastric Cancer

ISSN: 1436-3291

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-00V-BN6

DOI: 10.1007/s10120-021-01239-9

Abstract (EN): Background Tumour progression relies on the ability of cancer cells to penetrate and invade neighbouring tissues. E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell-cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM). Methods To identify ECM components and receptors relevant for adhesion of E-cadherin dysfunctional cells, we implemented a novel ECM microarray platform coupled with molecular interaction networks. The functional role of putative candidates was determined by combining micropattern traction microscopy, protein modulation and in vivo approaches, as well as transcriptomic data of 262 gastric carcinoma samples, retrieved from the cancer genome atlas (TCGA). Results Here, we show that E-cadherin mutations induce an abnormal interplay of cells with specific components of the ECM, which encompasses increased traction forces and Integrin beta 1 activation. Integrin beta 1 synergizes with E-cadherin dysfunction, promoting cell scattering and invasion. The significance of the E-cadherin-Integrin beta 1 crosstalk was validated in Drosophila models and found to be consistent with evidence from human gastric carcinomas, where increased tumour grade and poor survival are associated with low E-cadherin and high Integrin beta 1 levels. Conclusions Integrin beta 1 is a key mediator of invasion in carcinomas with E-cadherin impairment and should be regarded as a biomarker of poor prognosis in gastric cancer.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14