Prostate cancer (PCa) is a highly heterogeneous malignancy with variable clinical outcomes. Centrosomal protein 55 (CEP55) has been involved in the progression of multiple cancers, but its function in PCa is still largely uncharacterized. CEP55 expression was evaluated in clinical samples and cell lines via bioinformatics analysis, quantitative RT-PCR, and Western blot. Functional assessments, such as wound healing, Cell Counting Kit-8, and Transwell invasion, were carried out to evaluate the impact of CEP55 upregulation or knockdown on PCa cell growth and metastasis. Coimmunoprecipitation was utilized to observe the interaction between CEP55 and TPX2 microtubule nucleation factor. The role of CEP55 in ferroptosis regulation was assessed by measuring IC50 values of ferroptosis inducers, lipid reactive oxygen species levels, and the expression of ferroptosis-correlated proteins, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Xenograft tumor models were created to evaluate the in vivo effects of CEP55 suppression. CEP55 showed a significant upregulation in PCa tissues and cell lines. CEP55 overexpression was linked to advanced clinicopathological features and poor prognosis. Mechanistically, CEP55 interacted with TPX2 to activate the aurora kinase A (AURKA)-PI3K-AKT signaling cascade. This activation led to increased expression of SLC7A11 and GPX4, reduced lipid reactive oxygen species accumulation, and conferred resistance to ferroptosis. Pharmacological inhibition of the TPX2-AURKA interaction with CAM2602 reversed these effects. In vivo trials illustrated that CEP55 knockdown inhibited tumor growth and downregulated key proteins in the TPX2-AURKA-PI3K-AKT and ferroptosis resistance pathway. Our findings demonstrate that CEP55 enhances PCa progression by stimulating the TPX2-AURKA-PI3K-AKT signaling pathway and inhibiting ferroptosis. Targeting this axis may represent a potential therapeutic approach for PCa.
Xu et al. (Wed,) studied this question.