Intercepting YAP Activation in Prostate Cancer Blocks Neuroendocrine Progression - PubMed
4 hours ago
- #neuroendocrine
- #YAP activation
- #prostate cancer
- Neuroendocrine phenotype in castration-resistant prostate cancer (CRPC) is linked to poor prognosis.
- Castration-induced death of androgen-sensitive cells may promote interactions between rare androgen-independent cells and ECM, fostering neuroendocrine PC (NEPC) development.
- Poorly differentiated PC cells (PAC and PNE) interact with decellularized prostate ECM, enhancing PNE invasiveness via integrin α2 upregulation and YAP activation.
- RANK/RANKL and NF-κB inhibition prevents integrin α2 upregulation in PNE cells; integrin α2β1 and YAP inhibition reduces invasiveness.
- YAP-dependent metastatic behavior in PNE cells is observed in vivo; YAP inhibition suppresses NEPC and metastasis in mice.
- YAP inhibitors also inhibit growth of human CRPC organoids, suggesting therapeutic potential.
- The integrin α2-YAP axis is identified as a promising therapeutic target for PC patients undergoing androgen-deprivation therapy.