TY - JOUR
T1 - The two faces of Hippo
T2 - Targeting the Hippo pathway for regenerative medicine and cancer treatment
AU - Johnson, Randy
AU - Halder, Georg
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
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U2 - 10.1038/nrd4161
DO - 10.1038/nrd4161
M3 - Review article
C2 - 24336504
AN - SCOPUS:84891748709
SN - 1474-1776
VL - 13
SP - 63
EP - 79
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 1
ER -