Mammalian Hippo pathway: from development to cancer and beyond

The Hippo pathway was discovered as a signal transduction pathway that regulates organ size in Drosophila melanogaster. It is composed of three components: cell surface upstream regulators including cell adhesion molecules and cell polarity complexes; a kinase cascade comprising two serine-threonine kinases with regulators and adaptors; and a downstream target, a transcription coactivator. The coactivator mediates the transcription of cell proliferation-promoting and anti-apoptotic genes. The pathway negatively regulates the coactivator to restrict cell proliferation and to promote cell death. Thus, the pathway prevents tissue overgrowth and tumourigenesis. The framework of the pathway is conserved in mammals. A dysfunction of the pathway is frequently detected in human cancers and correlates with a poor prognosis. Recent works indicated that the Hippo pathway plays an important role in tissue homoeostasis through the regulation of stem cells, cell differentiation and tissue regeneration.