Work

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

Year: 2025

Type: article

Abstract: 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 ( CEP55 ) as a critical factor in the transformation from hormone-sensitive prostate cancer (HSPC) to CRPC and, ultimately, NEPC. Subsequent bioinformatics analyses and validation with clinical samples demonstrated that CEP55 is significantly upregulated in NEPC tissues compared to HSPC and CRPC. Furthermore, while CEP55 does not appear to be associated with the immune microenvironment or cancer-associated fibroblasts (CAFs), our findings indicate that it directly mediates the plasticity of prostate cancer cells, thereby promoting NEPC progression. Specifically, in vivo and in vitro experiments confirmed that CEP55 enhances cell proliferation, migration, and invasion and the expression of NEPC biomarkers in prostate cancer. Importantly, although cisplatin is the primary treatment for NEPC clinically, CEP55 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.

Source: Cancer Pathogenesis and Therapy

DOI: 10.1016/j.cpt.2025.06.008