Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression

Abstract

Biophysical cues, such as mechanical properties, play a critical role in tissue growth and homeostasis. During organ development and tissue injury repair, compressive and tensional forces generated by cell-extracellular matrix or cell-cell interaction are key factors for cell fate determination. In the vascular system, hemodynamic forces, shear stress, and cyclic stretch modulate vascular cell phenotypes and susceptibility to atherosclerosis. Despite that emerging efforts have been made to investigate how mechanotransduction is involved in tuning cell and tissue functions in various contexts, the regulatory mechanisms remain largely unknown. One of the challenges is to understand the signaling cascades that transmit mechanical cues from the plasma membrane to the cytoplasm and then to the nuclei to generate mechanoresponsive transcriptomes. YAP and its homolog TAZ, the Hippo pathway effectors, have been identified as key mechanotransducers that sense mechanical stimuli and relay the signals to control transcriptional programs for cell proliferation, differentiation, and transformation. However, the upstream mechanosensors for YAP/TAZ signaling and downstream transcriptome responses following YAP/TAZ activation or repression have not been well characterized. Moreover, the mechanoregulation of YAP/TAZ in literature is highly context-dependent. In this review, we summarize the biomechanical cues in the tissue microenvironment and provide an update on the roles of YAP/TAZ in mechanotransduction in various physiological and pathological conditions.

Targeting Mechanosensitive Piezo1 Alleviated Renal Fibrosis Through p38MAPK-YAP Pathway

“…Furthermore, YAP binds to transcriptional enhanced associate domain (TEAD) in the nucleus, which affects target gene such as CTGF and then cell proliferation and differentiation, tissue regeneration and organ size determination (Zhang et al, 2014;Brusatin et al, 2018). It has been reported that increased ECM stiffness activates YAP, which leads to ECM deposition and then contributes to increased ECM stiffness (Cai et al, 2021). Despite these important findings, the molecular mechanisms by which MCs sense and transduce the mechanical signals to activate YAP needs to be further explored.…”

Effects of Mechanical Stress Stimulation on Function and Expression Mechanism of Osteoblasts

“…Similarly, RhoA feels high ECM stiffness through focal adhesion, promotes actin polymerization and stress fiber formation, transmits stiffness signals to YAP/ TAZ, and regulates the sensitivity of osteoblasts (Wagh et al, 2021). MRTF and YAP/TAZ have been confirmed as transcription factors activated by mechanical induction (Finch-Edmondson and Sudol, 2016;Cai et al, 2021). The activity of ROCK is positively correlated with ECM stiffness.…”

Physical Forces and Transient Nuclear Envelope Rupture during Metastasis: The Key for Success?

“…One of the most characterized mechanosensitive pathways is the Hippo pathway and its components YAP and TAZ that interact with FA [ 36 , 37 ]. Another mechanosensitive sensor and transducer of mechanical stress is the calcium-permeable Piezo channel [ 38 ], located at the plasmatic membrane, which can assist the cell in choosing the migration pattern under a certain level of pressure and can shift movements using blebs rather than pseudopods [ 39 ].…”