Cell

Hippo signaling pathway

Computer network

Biology

Extracellular matrix

Upstream and downstream (DNA)

Regeneration (biology)

Upstream (networking)

Extracellular

Computer science

Cell growth

Signal transduction

Cell biology

Genetics

Nature Cell Biology

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. Stefano Piccolo and co-authors review recent insights into how YAP and TAZ transcription factors respond to the tissue environment, and how they mediate altered cell behaviour. Feedback mechanisms and crosstalk with other pathways are discussed, as are outstanding questions in the field.

YAP/TAZ upstream signals and downstream responses