Integrins Can Act As Suppressors of Ras-Mediated Oncogenesis in the Wing Disc Epithelium
Overview
Affiliations
Cancer is the second leading cause of death worldwide. Key to cancer initiation and progression is the crosstalk between cancer cells and their microenvironment. The extracellular matrix (ECM) is a major component of the tumour microenvironment and integrins, main cell-ECM adhesion receptors, are involved in every step of cancer progression. However, accumulating evidence has shown that integrins can act as tumour promoters but also as tumour suppressor factors, revealing that the biological roles of integrins in cancer are complex. This incites a better understating of integrin function in cancer progression. To achieve this goal, simple model organisms, such as , offer great potential to unravel underlying conceptual principles. Here, we find that in the wing disc epithelium the βPS integrins act as suppressors of tumours induced by a gain of function of the oncogenic form of , . We show that βPS integrin depletion enhances the growth, delamination and invasive behaviour of tumour cells, as well as their ability to affect the tumour microenvironment. These results strongly suggest that integrin function as tumour suppressors might be evolutionarily conserved. can be used to understand the complex tumour modulating activities conferred by integrins, thus facilitating drug development.
Local weakening of cell-extracellular matrix adhesion triggers basal epithelial tissue folding.
Valencia-Exposito A, Khalilgharibi N, Martinez-Abarca Millan A, Mao Y, Martin-Bermudo M EMBO J. 2025; .
PMID: 39962267 DOI: 10.1038/s44318-025-00384-6.