Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer

被引：58

作者：

da Silva, Elisabete Cruz ^{[1
]}

Dontenwill, Monique ^{[1
]}

Choulier, Laurence ^{[1
]}

Lehmann, Maxime ^{[1
]}

机构：

[1] Univ Strasbourg, Fac Pharm, Lab Bioimagerie & Pathol Tumoral Signaling & Ther, UMR 7021,CNRS, F-67401 Illkirch Graffenstaden, France

来源：

CANCERS | 2019年 / 11卷 / 05期

关键词：

integrin; focal adhesion kinase; therapy resistance; tyrosine kinase inhibitors; cancer-associated fibroblasts; mechanotransduction; EGFR; c-MET; ALPHA-V INTEGRIN; NEWLY-DIAGNOSED GLIOBLASTOMA; CELL CARCINOMA-CELLS; BREAST-CANCER; DRUG-RESISTANCE; EGF RECEPTOR; OPEN-LABEL; ALPHA-6-BETA-4; INTEGRIN; DRUGGABLE VULNERABILITY; ANTIANGIOGENIC THERAPY;

D O I：

10.3390/cancers11050692

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：27