Sox4 Regulates the Sensitivity of Canine Mammary Gland Tumor Cells to Cisplatin via the Wnt/β-catenin Signaling Pathway

Abstract

\n Background: The development of cisplatin resistance is one of the major causes of breast cancer treatment failure, and is associated with changes in Sox4 gene expression. In this study, a cisplatin-resistant cell line, CHMpCIS, was constructed from the cell line CHMp, which was isolated from the primary lesion of a malignant canine mammary gland tumor (CMGT). Sox4 expression was evaluated to assess its roles in cisplatin sensitivity, proliferation and apoptosis, epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) features, and activation of the Wnt/β-catenin signaling pathway in CMGT cells.Results: CHMpCIS Cells exhibited changes in morphology, slower proliferation, and greater anti-apoptotic ability, EMT and CSC features, and the Wnt/β-catenin pathway was activated in CHMpCIS cells. In CMGT tissues, Sox4 expression was elevated. In CHMpCIS cells, silencing Sox4 inhibited cisplatin resistance, EMT and CSC features, and Wnt/β-catenin signaling activation. Then activating the Wnt/β-catenin signaling pathway increased Sox4 expression levels.Conclusions: Silencing Sox4 inhibited the above-mentioned cancer cell characteristics in CHMpCIS cells compared with CHMp cells. In addition, activating the Wnt/β-catenin signaling pathway increased Sox4 expression levels, as part of a positive feedback loop. These findings may provide new targets and therapeutic strategies for the clinical treatment of CMGT as well as a reference for human mammary gland tumor (HMGT) research.