Neuroendocrine prostate cancer (NEPC)-associated centrosomal Protein 55 (CEP55) promotes cisplatin resistance in prostate cancer by regulating cyclin-dependent kinase 1 (CDK1) phosphorylation

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer (CRPC) that is typically resistant to nearly all current therapies. In this study, single-cell RNA sequencing (scRNA-seq) and dataset analyses identified Centrosomal Protein 55 (<i>CEP55</i>) as a critical factor in the transformation from hormone-sensitive prostate cancer (HSPC) to CRPC and, ultimately to, NEPC. Subsequent bioinformatics analyses and validation with clinical samples demonstrated that <i>CEP55</i> is significantly upregulated in NEPC tissues compared to HSPC and CRPC. Furthermore, while <i>CEP55</i> show no significant association with the immune microenvironment or cancer-associated fibroblasts (CAFs), our findings indicate that it directly mediates the plasticity of prostate cancer cells, thereby driving NEPC progression. Specifically, <i>in vivo</i> and <i>in vitro</i> experiments confirmed that <i>CEP55</i> enhances cell proliferation, migration, invasion and the expression of NEPC biomarkers in prostate cancer. Importantly, although cisplatin is the primary treatment for NEPC clinically, <i>CEP55</i> has been shown to regulate cisplatin resistance through the phosphorylation of CDK1 at the tyrosine 15 (Tyr15) site. In summary, our study identifies a key gene that influences the neuroendocrine differentiation process in prostate cancer, suggesting its potential as an important therapeutic target.