PIN1 enhances SUMOylation of YAP1 and inhibits ferroptosis via autophagy-dependent degradation of ACSL4 in cervical cancer

Cervical cancer (CC) is a prevalent malignancy threatening women’s health. Due to its complex pathogenesis and tumor heterogeneity, it is urgent to thoroughly investigate its pathological mechanisms. Based on the TCGA database, the expression and survival analysis of PIN1 and YAP1 were assessed in CC. To verify their roles in regulating CC, stable knockdown and overexpression cell lines were constructed in CC cell lines. In vivo and in vitro experiments were conducted to verify that PIN1 regulates YAP1’s SUMOylation levels and induces ACSL4’s autophagic degradation. This research shows that PIN1 binds to YAP1, promoting its SUMOylation and causing autophagy-mediated degradation of ACSL4, enabling cervical cancer cells to resist ferroptosis. In vivo xenograft models confirm these findings. This study identifies PIN1 as a key redox-balance node and presents it as a potential therapeutic target for CC ferroptosis. Inhibiting PIN1 and YAP1 can inhibit tumor progression, offering a promising approach for treating aggressive CC.