Integrins, CAFs and Mechanical Forces in the Progression of 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 alpha and beta 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.