Figure 1. YAP‐dependent transcriptional regulation drives cancer formation and metastasis.

Mechanical cues such as cell density, acto‐myosin contractility, or rigid ECM increase SKP2 expression through TEAD‐YAP activity, which subsequently assembles the Skp2/Skp1‐Cullin‐F‐box (SCF^{S kp2}) complex leading to degradation of the cell cycle inhibitors p21/p27. If YAP is inactivated, for example, when cells grow on soft substrates, SKP2 levels are low, p21/p27 proteins accumulate leading to cell cycle exit. Mechanical cues can also promote MRTF‐mediated recruitment of NCOA3 to the TEAD‐YAP complex, which can further strengthen the TEAD‐YAP‐mediated transcriptional activity.