Fig. 2.

Example of mechanoreciprocity. In this example (there are many molecular sensors, amplifiers and effectors of mechanics), an adherent cell senses an increase in ECM stiffness through integrins. This leads to an increase in focal adhesion formation and activation of focal adhesion kinase (FAK), which propagates the signal to mitogen-activated kinases, such as extracellular signal-regulated kinase (ERK), and the small GTPase Rho. In response to Rho activation, actomyosin contractility is elevated, causing the cell to become more spread and tightly adhered to its matrix. Additionally, transcription factors such as Yes-associated protein (YAP) are mechanically activated through Rho (Dupont et al., 2011), which induce the expression of ECM and ECM-modifying genes. Signaling downstream of ERK also results in transcriptional activation of proliferation and migration genes. In a physiological context, such as gastrulation or wound healing, this process is eventually resolved. In disease states, such as cancer, this cascade remains active, driving a vicious cycle of matrix stiffening and mechanosignaling, thereby contributing to disease progression.