CEP55 Drives Pancreatic Cancer Progression by Suppressing Ferroptosis

Pancreatic cancer (PC) remains a highly lethal malignancy with limited treatment options, largely due to its heterogeneity and therapy resistance. While ferroptosis-a form of iron-dependent cell death driven by lipid peroxidation-has emerged as a relevant pathway, its role in PC is incompletely understood, as is the oncogenic function of Centrosomal Protein 55 (CEP55). Here, we integrated TCGA data with immunohistochemical validation and demonstrated that CEP55 is significantly overexpressed in PC and correlates with advanced disease and poor prognosis. Functionally, CEP55 knockdown suppressed proliferation, migration, and clonogenicity, while inducing ferroptosis, as evidenced by elevated lipid peroxidation, iron accumulation, and glutathione depletion. Mechanistically, CEP55 silencing downregulated key ferroptosis suppressors, including GPX4, SLC7A11, and NQO1, increasing cellular sensitivity to ferroptotic stress. Erastin, a ferroptosis inducer, enhanced ferroptosis in CEP55-deficient cells and counteracted the tumor-promoting effects of CEP55 overexpression. In vivo, CEP55 silencing reduced tumor growth and altered ferroptosis markers. Our findings establish CEP55 as a novel driver of PC progression via ferroptosis suppression, supporting its potential as both a prognostic biomarker and a therapeutic target for combination strategies aimed at overcoming PC resistance.