FKBP9 Enhances Colon Cancer Cell Proliferation by Inhibiting GPX4 ‐Mediated Ferroptosis

Colorectal cancer, a major health issue worldwide, exhibits intricate molecular mechanisms that necessitate further exploration, particularly regarding regulated cell death pathways, such as ferroptosis. This study investigated the role of the immunophilin FKBP9 (FK506 Binding Protein 9) in colon cancer, specifically its effects on cell proliferation and ferroptosis resistance. Using molecular biology techniques, including quantitative reverse transcription PCR, Western blotting, and cell proliferation assays, we established that FKBP9 is overexpressed in colon cancer cell lines HCT116 and SW480. Furthermore, we demonstrated that FKBP9 enhances cell proliferation by inhibiting ferroptosis through glutathione peroxidase 4 (GPX4) expression upregulation, thereby reducing reactive oxygen species levels and stabilizing GPX4 by preventing its autophagic degradation. Notably, increased FKBP9 expression is associated with lower overall survival rates in patients with colon cancer, suggesting its potential as a prognostic marker. These findings underscore the therapeutic potential of FKBP9 in colon cancer, offering a new method to sensitize cancer cells to ferroptosis and improve patient outcomes.