Mechanotransduction at focal adhesions: from physiology to cancer development

Abstract

Living cells are continuously exposed to mechanical cues, and can translate these signals into biochemical information (e.g. mechanotransduction). This process is crucial in many normal cellular functions, e.g. cell adhesion, migration, proliferation, and survival, as well as the progression of diseases such as cancer. Focal adhesions are the major sites of interactions between extracellular mechanical environments and intracellular biochemical signalling molecules/cytoskeleton, and hence focal adhesion proteins have been suggested to play important roles in mechanotransduction. Here, we overview the current molecular understanding in mechanotransduction occurring at focal adhesions. We also introduce recent studies on how extracellular matrix and mechanical microenvironments contribute to the development of cancer.

Fig. 1

Focal adhesions. (A) Focal adhesions between a cell and extracellular matrix (ECM). (B) Structure and composition of focal adhesions. When bound to ECM (green), the transmembrane integrin receptor (red) can recruit signalling proteins (orange) and structural proteins (yellow), linking actomyosin fibres. (C) Actin stress fibres can be developed from focal adhesions, as visualized by GFP-actin and mCherry-paxillin staining in a mouse embryonic fibroblast cell. Scale bar = 10 μm.