The Hippo pathway is an evolutionarily conserved signalling pathway with key roles in organ development, epithelial homeostasis, tissue regeneration, wound healing and immune modulation. Many of these roles are mediated by the transcriptional effectors YAP and TAZ, which direct gene expression via control of the TEAD family of transcription factors. Dysregulated Hippo pathway and YAP/TAZ–TEAD activity is associated with various diseases, most notably cancer, making this pathway an attractive target for therapeutic intervention. This Review highlights the key findings from studies of Hippo pathway signalling across biological processes and diseases, and discusses new strategies and therapeutic implications of targeting this pathway.
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K.-L.G. is supported by grants from NIH (CA196878, CA217642, GM51586). X.V. is supported by grants from NIH (R01HL124392 and R21HD094012) and the American Cancer Society (130257-RSG-17-138-01-CSM). The authors acknowledge P. Cotelle for Fig. 3c,d, C. Noland for Fig. 3a and P. Calses for Fig. 4.
K.-L.G. is a co-founder and has an equity interest in Vivace Therapeutics, Inc. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. A.D. is an employee of Genentech and shareholder at Roche.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The process through which cells sense and respond to mechanical stimuli by converting them into biochemical signals for cellular signalling and responses.
- Cholestatic liver injury
A condition with reduced or blocked flow of bile from the liver.
The surgical removal of the lung or a lobe of the lung.
The impairment of cellular function caused by protein misfolding.
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Dey, A., Varelas, X. & Guan, KL. Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenerative medicine. Nat Rev Drug Discov 19, 480–494 (2020). https://doi.org/10.1038/s41573-020-0070-z
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