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The pathway that tells organs when to stop growing. Cancers disable it so YAP and TAZ stay in the nucleus driving growth; in mesothelioma, NF2 loss does exactly that, and the first drugs against the YAP-TEAD switch are in trials.
Mechanical and contact cues activate the Hippo kinases MST1/2-LATS1/2, which phosphorylate and exclude YAP/TAZ from the nucleus. NF2 (Merlin) loss (mesothelioma, meningioma), LATS loss, and YAP/TAZ fusions (epithelioid haemangioendothelioma) unleash YAP/TAZ-TEAD transcription. TEAD palmitoylation-pocket inhibitors (IK-930, VT3989, IAG933) are in phase 1/2, notably in NF2-mutant mesothelioma and as combinations to overcome KRAS/EGFR-inhibitor resistance, where YAP is a bypass route. YAP also drives stiffness-induced signalling and CAF activation.
A building inspector (Hippo) who checks that the block is full and stops new floors. Cancers fire the inspector, and the architect (YAP/TAZ) keeps adding storeys.
Shares Massachusetts General Hospital Cancer Center, Memorial Sloan Kettering Cancer Center, RAS / RAF / MEK / ERK (MAPK) and the tag mechanism.
Shares Invasion: proteases, adhesion & the invasive front, Epithelial-mesenchymal transition & drug efflux, Tumour microenvironment (TME), Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares Invasion: proteases, adhesion & the invasive front, Fibroblast activation, desmoplasia & matrix stiffness, Epithelial-mesenchymal transition & drug efflux, Tumour microenvironment (TME) and the tag mechanism.
Shares Memorial Sloan Kettering Cancer Center, RAS / RAF / MEK / ERK (MAPK), KRAS and the tag mechanism.
Shares Tumour microenvironment (TME), Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares Epithelial-mesenchymal transition & drug efflux, Memorial Sloan Kettering Cancer Center and the tag mechanism.
Shares RAS / RAF / MEK / ERK (MAPK), KRAS and the tag mechanism.
Shares Tumour microenvironment (TME), Memorial Sloan Kettering Cancer Center and the tag mechanism.