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Mechanobiology of YAP and TAZ in physiology and disease
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Journal Article
Mechanobiology of YAP and TAZ in physiology and disease
2017
Overview
Key Points
Mechanical signals are fundamental regulators of cell behaviour, but how mechanical cues are sensed and transduced at the molecular level to regulate gene expression has long remained enigmatic.
YAP and TAZ have been identified as conserved mechanotransducers, reading a very diverse set of mechanical cues, from shear stress to cell shape and extracellular matrix rigidity, and translating them into cell-specific transcriptional programmes.
YAP and TAZ mechanotransduction offers new means to interpret and study classic aspects of tissue physiology and pathology in molecular terms.
YAP and TAZ as mechanotransducers provide insight into how aberrant cell mechanics drive the onset of multiple diseases, including atherosclerosis, fibrosis, cardiac hypertrophy, muscular dystrophy and cancer.
The transcription factors YAP and TAZ have recently emerged as being conserved transducers of mechanical signals into cells and mediators of processes such as proliferation, migration and cell fate decision. The roles of YAP-mediated and TAZ-mediated mechanotransduction have now been documented in many physiological and pathological contexts, providing novel insights into cellular mechano-responses and their consequences.
A growing body of evidence suggests that mechanical signals emanating from the cell's microenvironment are fundamental regulators of cell behaviour. Moreover, at the macroscopic scale, the influence of forces, such as the forces generated by blood flow, muscle contraction, gravity and overall tissue rigidity (for example, inside of a tumour lump), is central to our understanding of physiology and disease pathogenesis. Still, how mechanical cues are sensed and transduced at the molecular level to regulate gene expression has long remained enigmatic. The identification of the transcription factors YAP and TAZ as mechanotransducers started to fill this gap. YAP and TAZ read a broad range of mechanical cues, from shear stress to cell shape and extracellular matrix rigidity, and translate them into cell-specific transcriptional programmes. YAP and TAZ mechanotransduction is critical for driving stem cell behaviour and regeneration, and it sheds new light on the mechanisms by which aberrant cell mechanics is instrumental for the onset of multiple diseases, such as atherosclerosis, fibrosis, pulmonary hypertension, inflammation, muscular dystrophy and cancer.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adaptor Proteins, Signal Transducing - genetics
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Atherosclerosis - metabolism
/ Cancer
/ Extracellular Matrix - genetics
/ Extracellular Matrix - metabolism
/ Extracellular Matrix - pathology
/ Fibrosis
/ Gravity
/ Humans
/ Hypertension, Pulmonary - genetics
/ Hypertension, Pulmonary - metabolism
/ Hypertension, Pulmonary - pathology
/ Mechanotransduction, Cellular
/ Muscular Dystrophies - genetics
/ Muscular Dystrophies - metabolism
/ Muscular Dystrophies - pathology
/ Phosphoproteins - metabolism
/ Rigidity
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Tumors
