Targeting P2Y14R inhibits proliferation of cervical cancer cells and organoids and activates cAMP/PKA/CREB signaling pathway.

Purinergic signaling has been widely recognized as a critical regulator of tumor progression, yet the role of P2Y14R in cervical cancer remains unclear. This study used the P2Y14R antagonist PPTN in in vitro cell experiments; the results showed that it significantly inhibited cell proliferation and increased LDH release. The anti-tumor effect of P2Y14R antagonism was further validated using a cervical cancer organoid model. Mechanistically, PPTN treatment elevated intracellular cAMP levels, enhanced the phosphorylation of PKA and CREB, and thereby activated the cAMP/PKA/CREB signaling axis. Moreover, PPTN intervention reduced Ki67 expression in cervical cancer organoids without affecting CK13 expression, suggesting that the anti-tumor effect of PPTN may not mediated through regulation of differentiation. Collectively, these findings identify P2Y14R as a novel regulator of the cAMP/PKA/CREB signaling pathway in cervical cancer cells, providing a promising therapeutic target for cervical cancer.