The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment

Nat Rev Drug Discov. 2014 Jan;13(1):63-79. doi: 10.1038/nrd4161. Epub 2013 Dec 13.


The Hippo signalling pathway is an emerging growth control and tumour suppressor pathway that regulates cell proliferation and stem cell functions. Defects in Hippo signalling and hyperactivation of its downstream effectors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) contribute to the development of cancer, which suggests that pharmacological inhibition of YAP and TAZ activity may be an effective anticancer strategy. Conversely, YAP and TAZ can also have beneficial roles in stimulating tissue repair and regeneration following injury, so their activation may be therapeutically useful in these contexts. A complex network of intracellular and extracellular signalling pathways that modulate YAP and TAZ activities have recently been identified. Here, we review the regulation of the Hippo signalling pathway, its functions in normal homeostasis and disease, and recent progress in the identification of small-molecule pathway modulators.

Publication types

  • Review

MeSH terms

  • Animals
  • Hippo Signaling Pathway
  • Homeostasis / physiology
  • Humans
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / physiopathology
  • Protein Serine-Threonine Kinases / drug effects*
  • Protein Serine-Threonine Kinases / physiology
  • Regeneration / drug effects*
  • Regeneration / physiology
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology


  • Protein Serine-Threonine Kinases