Extracellular matrix regulates lineage plasticity in prostate cancer through YAP/TEAD

Disruption of extracellular matrix-integrin-YAP/TEAD signaling triggers neuroendocrine lineage transition in prostate cancer, with significant implications for therapy resistance.

• Why it matters: Understanding mechanisms behind lineage plasticity in prostate cancer is crucial because NEPC is an emerging resistance mode to androgen receptor pathway inhibitors, limiting treatment options and patient outcomes.
• What they did: The study used genetic deletion of Itgb1 and pharmacological approaches to manipulate YAP1/TEAD activity, revealing how extracellular matrix signals regulate NEPC transition and identifying key molecular interactions.
• The result: Restoring YAP1/TEAD signaling prevents NEPC transition, suggesting that targeting this pathway could modulate lineage plasticity and improve therapeutic strategies against resistant prostate cancers.