The roles of integrins in cancer

Fac Rev. 2021 May 7:10:45. doi: 10.12703/r/10-45. eCollection 2021.

Abstract

Integrin-mediated adhesion of cells to the extracellular matrix (ECM) is crucial for the physiological development and functioning of tissues but is pathologically disrupted in cancer. Indeed, abnormal regulation of integrin receptors and ECM ligands allows cancer cells to break down tissue borders, breach into blood and lymphatic vessels, and survive traveling in suspension through body fluids or residing in metabolically or pharmacologically hostile environments. Different molecular and cellular mechanisms responsible for the modulation of integrin adhesive function or mechanochemical signaling are altered and participate in cancer. Cancer development and progression are also bolstered by dysfunctionalities of integrin-mediated ECM adhesion occurring both in tumor cells and in elements of the surrounding tumor microenvironment, such as vascular cells, cancer-associated fibroblasts, and immune cells. Mounting evidence suggests that integrin inhibitors may be effectively exploited to overcome resistance to standard-of-care anti-cancer therapies.

Keywords: Integrins; cancer.

Publication types

  • Review

Grants and funding

Work in the authors’ laboratories was supported by Fondazione AIRC IG grants #13016, #16702, and #21315 (to GS) and #20366 (to DV); Fondazione AIRC under 5 per Mille 2018 - ID. 21052 program – P.I. Comoglio Paolo, G.L. Serini Guido (to GS); FPRC-ONLUS grant “MIUR 2010 Vaschetto - 5 per mille 2010 MIUR” (to GS); Telethon Italy (GGP09175) (to GS); and Associazione “Augusto per la Vita” (to GS).