MISP Suppresses Ferroptosis via MST1/2 Kinases to Facilitate YAP Activation in Non-Small Cell Lung Cancer.

ABSTRACT: Despite advances in non-small cell lung cancer (NSCLC) therapies, resistance remains a major challenge. Ferroptosis, a form of regulated cell death, plays a key role in cancer progression and treatment response. However, the mechanisms governing ferroptosis in NSCLC are not fully understood. The Hippo pathway, which regulates cell proliferation, has recently been implicated in ferroptosis regulation. In this study, we identify Mitotic Spindle Positioning (MISP) as a critical inhibitor of ferroptosis in NSCLC. MISP is upregulated in NSCLC tissues, and its loss sensitizes cells to ferroptosis, reducing cell proliferation in vitro and in vivo. Mechanistically, MISP binds to the SARAH domain of MST1/2 kinases, inhibiting their homodimerization and autophosphorylation, leading to sustained acti

SUBMITTER: Zhang F 

PROVIDER: S-EPMC12021056 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature