MAD2L1 overexpression promotes breast cancer progression and confers resistance to paclitaxel via proteasomal stabilization.

Mitotic arrest deficiency protein 2-like 1 (MAD2L1) is a notable component of the spindle assembly checkpoint that ensures proper chromosome segregation during mitosis. Analysis of The Cancer Genome Atlas breast cancer datasets revealed that MAD2L1 expression was markedly upregulated in tumor tissues and was associated with advanced clinical stages, lymph node metastasis and poor overall survival. To investigate these findings, in vitro functional assays, flow cytometry, western blotting, protein stability assays and paclitaxel sensitivity treatments were performed. Functional experiments demonstrated that MAD2L1 overexpression promoted breast cancer cell proliferation and colony formation, reduced G2/M phase accumulation and increased the protein levels of cyclin A and CDK1. MAD2L1 exerted these effects through inhibition of proteasomal degradation rather than through transcriptional regulation, suggesting that MAD2L1 stabilized key cell cycle regulators to sustain proliferation. Furthermore, MAD2L1 attenuated the cytotoxic effects of paclitaxel by counteracting drug-induced G2/M phase arrest and apoptosis, thereby diminishing the chemotherapeutic response. Collectively, the present findings indicated that MAD2L1 drove breast cancer progression and contributed to paclitaxel resistance via proteasomal stabilization of cyclin A and CDK1, underscoring its potential as a prognostic biomarker and therapeutic target in breast cancer.