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Integrins, CAFs and Mechanical Forces in the Progression of Cancer

Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA
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Cancers 2019, 11(5), 721; https://doi.org/10.3390/cancers11050721
Received: 19 April 2019 / Revised: 17 May 2019 / Accepted: 20 May 2019 / Published: 24 May 2019
(This article belongs to the Special Issue The Role of Integrins in Cancer)
Cells respond to both chemical and mechanical cues present within their microenvironment. Various mechanical signals are detected by and transmitted to the cells through mechanoreceptors. These receptors often contact with the extracellular matrix (ECM), where the external signals are converted into a physiological response. Integrins are well-defined mechanoreceptors that physically connect the actomyosin cytoskeleton to the surrounding matrix and transduce signals. Families of α and β subunits can form a variety of heterodimers that have been implicated in cancer progression and differ among types of cancer. These heterodimers serve as the nexus of communication between the cells and the tumor microenvironment (TME). The TME is dynamic and composed of stromal cells, ECM and associated soluble factors. The most abundant stromal cells within the TME are cancer-associated fibroblasts (CAFs). Accumulating studies implicate CAFs in cancer development and metastasis through their remodeling of the ECM and release of large amounts of ECM proteins and soluble factors. Considering that the communication between cancer cells and CAFs, in large part, takes place through the ECM, the involvement of integrins in the crosstalk is significant. This review discusses the role of integrins, as the primary cell-ECM mechanoreceptors, in cancer progression, highlighting integrin-mediated mechanical communication between cancer cells and CAFs. View Full-Text
Keywords: integrin; CAF; cancer-associated fibroblast; cancer cells; mechanics of cancer; mechanotransduction; TME; tumor microenvironment; ECM; extracellular matrix; ECM remodeling; ECM proteins integrin; CAF; cancer-associated fibroblast; cancer cells; mechanics of cancer; mechanotransduction; TME; tumor microenvironment; ECM; extracellular matrix; ECM remodeling; ECM proteins
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Jang, I.; Beningo, K.A. Integrins, CAFs and Mechanical Forces in the Progression of Cancer. Cancers 2019, 11, 721.

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