Contact inhibition
Normal cells stop dividing when they touch neighbours or feel a stiff, crowded tissue. The Hippo pathway relays that signal by locking YAP/TAZ out of the nucleus. Tumours ignore the crowd.
Diagram
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
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.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 1, The body's defences: Cancer is not the default.
Normal cells stop dividing when they touch neighbours or feel a stiff, crowded tissue. The Hippo pathway relays that signal by locking YAP/TAZ out of the nucleus. Tumours ignore the crowd.
Hippo-YAP/TAZ. 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.
The molecular players
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
No target record is listed at this stage or drawn in its diagrams; the pathways above carry the mechanism.
Where medicines act
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
No product in the corpus acts on a target at this stage yet.
Open questions
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
- Are TEAD inhibitors tolerable and active beyond NF2-mutant mesothelioma?
- How much of drug tolerance is YAP-driven and reversible?
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2023reviewInsights into recent findings and clinical application of YAP and TAZ in cancerNature Reviews Cancer
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 1.7 of 56.