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

UMR 7021 CNRS, Laboratoire de Bioimagerie et Pathologies, Tumoral Signaling and Therapeutic Targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch, France
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Cancers 2019, 11(5), 692; https://doi.org/10.3390/cancers11050692
Received: 15 April 2019 / Revised: 13 May 2019 / Accepted: 14 May 2019 / Published: 17 May 2019
(This article belongs to the Special Issue The Role of Integrins in Cancer)
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Abstract

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. View Full-Text
Keywords: integrin; focal adhesion kinase; therapy resistance; tyrosine kinase inhibitors; cancer-associated fibroblasts; mechanotransduction; EGFR; c-MET integrin; focal adhesion kinase; therapy resistance; tyrosine kinase inhibitors; cancer-associated fibroblasts; mechanotransduction; EGFR; c-MET
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Cruz da Silva, E.; Dontenwill, M.; Choulier, L.; Lehmann, M. Role of Integrins in Resistance to Therapies Targeting Growth Factor Receptors in Cancer. Cancers 2019, 11, 692.

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