Ovarian cancer (OV) is a highly metastatic and recurrent malignancy with limited therapeutic options. NIMA-related kinase 1 (NEK1), a serine/threonine kinase implicated in cell cycle regulation and DNA damage response, has been associated with tumorigenesis in various cancers, yet its specific role in OV pathogenesis remains elusive. This study systematically investigates the oncogenic function and underlying mechanisms of NEK1 in ovarian cancer. Our findings demonstrate that NEK1 promotes tumor progression both in vitro and in vivo. Mechanistically, bioinformatic and biochemical analyses reveal that NEK1 suppresses p53 signaling activity, resulting in downregulation of downstream targets p21 and PUMA, consequently attenuating cell cycle arrest and apoptosis. Importantly, NEK1-driven oncogenicity is dependent on the presence of p53 protein. Clinically, elevated NEK1 expression significantly correlates with poorer prognosis across multiple independent OV cohorts. Paradoxically, high NEK1 expression enhances radiosensitivity by impairing p53-mediated DNA damage repair. Collectively, these findings establish NEK1 as a promising prognostic biomarker and therapeutic target, with potential utility in guiding genotoxic therapy strategies for ovarian cancer patients.
Song et al. (Thu,) studied this question.