Ferroptosis triggers anti-tumor immunity via promoting chaperone-mediated autophagic degradation of SHP2.

ABSTRACT: Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, plays a significant role in various physiological and pathological processes, including cancer. However, the connection between ferroptosis and anti-tumor immunity remains incompletely understood. Our investigation demonstrates that ferroptosis inducers like RSL3 can enhance the efficacy of anti-PD-1 therapy by activating the STAT1 signaling pathway. Mechanistically, RSL3 activates the tyrosine phosphatase SHP2 in cancer cells and facilitates its degradation through chaperone-mediated autophagy mediated by the KFERQ motif from residues 530 to 534. This enhances cancer cells' sensitivity to IFN-γ, leading to increased phosphorylation and nuclear translocation of STAT1 and higher expression of maj

SUBMITTER: Zhu J 

PROVIDER: S-EPMC12375215 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature