P23 acts as a negative regulator of ferroptosis in NSCLC by blocking GPX4 degradation via chaperone-mediated autophagy.

ABSTRACT: Ferroptosis has been identified as a tumor-inhibiting event in a variety of cancers; however, its molecular basis in non-small cell lung cancer (NSCLC) has not been completely elucidated. Notably, glutathione peroxidase 4 (GPX4) plays a crucial role in ferroptosis. Our previous research revealed that prostaglandin E synthase 3 (p23), a potential transcription factor, plays a crucial role in promoting cancer progression and metastasis through succinylation. Our study revealed a previously unknown antiferroptotic function of p23. Mechanistically, p23 stabilizes GPX4 by competitively binding heat shock cognate 71 kDa protein (HSC70) to suppress chaperone-mediated autophagy (CMA) activity, which subsequently inhibits ferroptosis and accelerates tumor growth. Notably, impairing p23 succinylatio

SUBMITTER: Chen J 

PROVIDER: S-EPMC12492921 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature