Regulation of Hippo Signaling by Mechanical Signals and the Cytoskeleton

Hippo signaling regulates the balance between cell proliferation and apoptosis to control the size of organs during development. Appropriate Hippo signaling is associated with stem cell differentiation, and inappropriate signaling can result in tumorigenesis and cancer. Hippo signaling activity is influenced not only by biochemical signals but also by mechanical force and the cytoskeleton transmitted through cell–cell junctions and cell–matrix adhesions. In this review, we describe the evidence for the regulation of Hippo signaling by the spatial reorganization of signaling components, mechanical force, and the cytoskeleton. Although our understanding of the relationship between Hippo signal transduction and mechanical force and the cytoskeleton is developing rapidly, many unresolved questions remain.