YAP/TAZ upstream signals and downstream responses

Abstract

Cell behaviour is strongly influenced by physical, mechanical contacts between cells and their extracellular matrix. We review how the transcriptional regulators YAP and TAZ integrate mechanical cues with the response to soluble signals and metabolic pathways to control multiple aspects of cell behaviour, including proliferation, cell plasticity and stemness essential for tissue regeneration. Corruption of cell-environment interplay leads to aberrant YAP and TAZ activation that is instrumental for multiple diseases, including cancer.

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Fig. 1: Biomechanical signal transduction to YAP/TAZ.
Fig. 2: YAP/TAZ regulation by Hippo and Wnt signalling.
Fig. 3: YAP/TAZ nuclear activities and positive feedback mechanisms.

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Acknowledgements

The authors thank all members of the S.P. laboratory for discussion. This work is supported by AIRC Special Program Molecular Clinical Oncology ‘5 per mille’, by an AIRC PI-Grant to S.P., and by Epigenetics Flagship project CNR-MIUR grants to S.P, and from a donation in memoriam of Liana Simonutti. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 670126-DENOVOSTEM).

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Totaro, A., Panciera, T. & Piccolo, S. YAP/TAZ upstream signals and downstream responses. Nat Cell Biol 20, 888–899 (2018). https://doi.org/10.1038/s41556-018-0142-z

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