# Hippo-YAP/TAZ

Source: https://onco.cc/pathways/hippo-yap/  
OnCo record `hippo-yap` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- 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.
- 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

## Notes

- Leading programmes: Camargo (Stanford), Guan (UCSD), Pan (Johns Hopkins) on Hippo biology; Vivace Therapeutics, Ikena, Novartis on TEAD inhibitors.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Hippo_signaling_pathway
- Franklin, Wu & Guan, Insights into recent findings and clinical application of YAP and TAZ in cancer (Nature Reviews Cancer 2023): https://doi.org/10.1038/s41568-023-00579-1

## Connected records

- cancers: [Ependymoma](https://onco.cc/cancers/ependymoma/), [Mesothelioma](https://onco.cc/cancers/mesothelioma/), [Vascular tumours (angiosarcoma, epithelioid haemangioendothelioma, kaposiform haemangioendothelioma)](https://onco.cc/cancers/vascular-tumours/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [KRAS](https://onco.cc/targets/kras/), [LATS1](https://onco.cc/targets/lats1/), [NF2](https://onco.cc/targets/nf2/), [YAP1](https://onco.cc/targets/yap1/)
- institutions: [Massachusetts General Hospital Cancer Center](https://onco.cc/institutions/mgh/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/), [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Invasion: proteases, adhesion & the invasive front](https://onco.cc/pathways/invasion-ecm-degradation/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- key papers: [Insights into recent findings and clinical application of YAP and TAZ in cancer](https://onco.cc/key-papers/paper-franklin-nat-rev-cancer/)
- terms: [Hallmark: evading growth suppressors](https://onco.cc/terms/evading-growth-suppressors/), [Mechanical theory: stiffness, pressure and force as causes](https://onco.cc/terms/mechanical-theory-of-cancer/)

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JSON: https://onco.cc/api/v1/entities/hippo-yap.json