DSN1 promotes breast cancer proliferation and tumor growth through activation of the CDC25C/CDK1/Cyclin B1 signaling axis

Breast cancer is the most prevalent malignancy among women. Dysregulation of mitotic checkpoint proteins drives uncontrolled proliferation and tumor progression. DSN1, a kinetochore-associated protein and key component of the Mis12 complex, plays an essential role in chromosome segregation, but its function in breast cancer remains unclear. DSN1 expression in breast cancer was analyzed using GEPIA and Kaplan–Meier Plotter databases, and validated by qPCR and Western blot in normal and cancer cell lines. Functional assays (CCK-8, colony formation, EdU incorporation, and flow cytometry) were performed in MDA-MB-468, MDA-MB-231, and BT-20 cells to assess proliferation, cell cycle, and apoptosis. The CDC25C/CDK1/Cyclin B1 pathway was evaluated by Western blot, phosphorylation analysis, pharmacological inhibition, and CDC25C knockdown experiments. The oncogenic role of DSN1 was confirmed in xenograft nude mouse models. DSN1 expression was significantly upregulated in breast cancer tissues and cell lines and correlated with poor overall and relapse-free survival. DSN1 overexpression enhanced proliferation and was associated with reduced apoptotic markers, whereas its knockdown exerted the opposite effects. Mechanistically, DSN1 promoted G2/M transition in a manner dependent on the CDC25C/CDK1/Cyclin B1 axis. Inhibition or knockdown of CDC25C abrogated DSN1-induced proliferation and cell cycle activation. In vivo, DSN1 overexpression accelerated tumor growth and increased Ki-67 expression. DSN1 acts as a novel oncogenic regulator in triple-negative and basal-like breast cancer, promoting cell proliferation and tumor growth in a manner dependent on the CDC25C/CDK1/Cyclin B1 signaling pathway. These findings highlight DSN1 as a potential prognostic biomarker in breast cancer, although its oncogenic role in luminal and HER2-positive subtypes remains to be further investigated.