Cruz da Silva Elisabete, Dontenwill Monique, Choulier Laurence, Lehmann Maxime
UMR 7021 CNRS, Laboratoire de Bioimagerie et Pathologies, Tumoral Signaling and Therapeutic Targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch, France.
Cancers (Basel). 2019 May 17;11(5):692. doi: 10.3390/cancers11050692.
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.
整合素通过激活细胞内信号转导通路和传递机械张力来促进癌症进展和侵袭性。值得注意的是，这些黏附受体与受体酪氨酸激酶（RTK）共享共同的信号网络，并支持其致癌活性，从而促进癌细胞增殖、存活和侵袭。在过去十年中，临床前研究表明，整合素在对靶向RTK及其下游通路的疗法的耐药性中起重要作用。整合素的一个显著特征是它们与RTK广泛的相互联系，这有助于癌细胞适应并更好地在治疗中存活。在这种情况下，我们不仅应考虑癌细胞中表达的整合素，还应考虑基质细胞中表达的整合素，因为这些整合素可机械性地增加肿瘤微环境的硬度并赋予治疗耐药性。本综述介绍了其中一些机制，并概述了提高靶向RTK信号疗法疗效的新治疗选择。
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