YB-1 drives triple-negative breast cancer progression and paclitaxel resistance through Wnt/β-catenin pathway.

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer. While chemotherapy remains the cornerstone of TNBC treatment, the frequent development of drug resistance often results in unfavorable clinical outcomes. Y-box binding protein-1 (YB-1) has been implicated in cancer progression and drug resistance, but its specific role and mechanisms in TNBC are poorly understood. This study investigates the impact of YB-1 on TNBC progression and paclitaxel resistance. Tumor and adjacent normal tissues were collected from 10 patients with TNBC to evaluate YB-1 expression. Cell viability, proliferation, and apoptosis were assessed using the CCK-8 assay, EdU staining, and flow cytometry, respectively. A xenograft model was employed to monitor tumor growth, while protein levels were analyzed using western blotting and immunohistochemistry. Elevated YB-1 expression was observed in TNBC tissues and cells. Functional assays revealed that YB-1 overexpression enhanced TNBC cell proliferation, inhibited apoptosis, and heightened resistance to paclitaxel in vitro. Conversely, YB-1 suppression yielded the opposite effects. Mechanistically, YB-1 overexpression was associated with enhanced Wnt/β-catenin pathway activity, which functionally contributed to increased paclitaxel resistance. Similar effects were confirmed in vivo, where YB-1 overexpression accelerated tumor growth, increased paclitaxel resistance, and activated the Wnt/β-catenin pathway, whereas YB-1 suppression reversed these outcomes. In conclusion, YB-1 facilitates TNBC cell proliferation, suppresses apoptosis, and strengthens paclitaxel resistance through activation of the Wnt/β-catenin pathway. These findings highlight YB-1 as a promising therapeutic target for TNBC treatment.