{"entity":{"id":"hippo-yap","kind":"pathway","name":"Hippo-YAP/TAZ","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Hippo_signaling_pathway","links":[{"label":"Franklin, Wu & Guan, Insights into recent findings and clinical application of YAP and TAZ in cancer (Nature Reviews Cancer 2023)","url":"https://doi.org/10.1038/s41568-023-00579-1"}],"tags":["mechanism"],"related":[],"cancers":["mesothelioma"],"sections":[],"technologies":[],"targets":["kras","egfr"],"drugs":[],"companies":[],"institutions":["mgh","mskcc"],"pathways":["ras-mapk","emt","tumor-microenvironment"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-franklin-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":["Leading programmes: Camargo (Stanford), Guan (UCSD), Pan (Johns Hopkins) on Hippo biology; Vivace Therapeutics, Ikena, Novartis on TEAD inhibitors."],"analogy":"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.","nodes":[{"id":"cue","label":"Contact, stiffness, GPCRs","x":12,"y":40},{"id":"nf2","label":"NF2 (Merlin)","x":32,"y":20},{"id":"mst","label":"MST1/2 → LATS1/2","x":50,"y":40},{"id":"yap","label":"YAP/TAZ","x":70,"y":40},{"id":"tead","label":"TEAD transcription","x":88,"y":40},{"id":"out","label":"Growth, EMT, drug tolerance","x":88,"y":80}],"edges":[{"from":"cue","to":"mst","type":"activates"},{"from":"nf2","to":"mst","type":"activates"},{"from":"mst","to":"yap","type":"inhibits"},{"from":"yap","to":"tead","type":"activates"},{"from":"tead","to":"out","type":"activates"}],"interventions":["TEAD inhibitors (VT3989, IK-930, IAG933) in NF2-mutant mesothelioma and with KRAS/EGFR inhibitors","Verteporfin repurposing (preclinical)","Combination rationale: YAP bypass after MAPK inhibition"]},"route":"/pathways/hippo-yap/","neighbours":{"cancer":[{"id":"ependymoma","kind":"cancer","name":"Ependymoma","route":"/cancers/ependymoma/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"vascular-tumours","kind":"cancer","name":"Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)","route":"/cancers/vascular-tumours/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"lats1","kind":"target","name":"LATS1","route":"/targets/lats1/"},{"id":"nf2","kind":"target","name":"NF2","route":"/targets/nf2/"},{"id":"yap1","kind":"target","name":"YAP1","route":"/targets/yap1/"}],"institution":[{"id":"mgh","kind":"institution","name":"Massachusetts General Hospital Cancer Center","route":"/institutions/mgh/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"emt","kind":"pathway","name":"Epithelial-mesenchymal transition & drug efflux","route":"/pathways/emt/"},{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"invasion-ecm-degradation","kind":"pathway","name":"Invasion: proteases, adhesion & the invasive front","route":"/pathways/invasion-ecm-degradation/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"paper":[{"id":"paper-franklin-nat-rev-cancer","kind":"paper","name":"Insights into recent findings and clinical application of YAP and TAZ in cancer","route":"/key-papers/paper-franklin-nat-rev-cancer/"}],"term":[{"id":"evading-growth-suppressors","kind":"term","name":"Hallmark: evading growth suppressors","route":"/terms/evading-growth-suppressors/"},{"id":"mechanical-theory-of-cancer","kind":"term","name":"Mechanical theory: stiffness, pressure and force as causes","route":"/terms/mechanical-theory-of-cancer/"}]}}