Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer.
Fiche publication
Date publication
mai 2019
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHOULIER Laurence, Dr DONTENWILL Monique, Pr LEHMANN Maxime
Tous les auteurs :
Cruz da Silva E, Dontenwill M, Choulier L, Lehmann M
Lien Pubmed
Résumé
Integrins contribute to cancer progression and aggressiveness by activating intracellular signal transduction pathways and transducing mechanical tension forces. Remarkably, these adhesion receptors share common signaling networks with receptor tyrosine kinases (RTKs) and support their oncogenic activity, thereby promoting cancer cell proliferation, survival and invasion. During the last decade, preclinical studies have revealed that integrins play an important role in resistance to therapies targeting RTKs and their downstream pathways. A remarkable feature of integrins is their wide-ranging interconnection with RTKs, which helps cancer cells to adapt and better survive therapeutic treatments. In this context, we should consider not only the integrins expressed in cancer cells but also those expressed in stromal cells, since these can mechanically increase the rigidity of the tumor microenvironment and confer resistance to treatment. This review presents some of these mechanisms and outlines new treatment options for improving the efficacy of therapies targeting RTK signaling.
Mots clés
EGFR, c-MET, cancer-associated fibroblasts, focal adhesion kinase, integrin, mechanotransduction, therapy resistance, tyrosine kinase inhibitors
Référence
Cancers (Basel). 2019 May 17;11(5):