The tumor suppressor SALL2 opposes chemotherapeutic resistance in breast cancer

Chemotherapy continues to be the primary treatment for certain types of breast cancer. However, despite an initial positive response to chemotherapeutic agents, the development of resistance is inevitable. The exact molecular mechanisms underlying this phenomenon remain unclear. In this research, a significant downregulation of SALL2 expression was observed in chemo-resistant breast cancer, which was attributed to promoter methylation. Decreased SALL2 expression correlated significantly with poorer relapse-free survival in chemotherapy-treated patients with breast cancer. Functionally, SALL2 silencing induced a stem cell-like phenotype in breast cancer cells, fostering resistance to cisplatin both in vitro and in vivo. This resistance was mediated, at least in part, through the transcriptional regulation of BTG2, a negative regulator of stemness, achieved by direct binding to its promoter regions. These findings underscore the critical role of SALL2 in modulating cisplatin response and propose SALL2 as a potential prognostic biomarker for chemotherapy response in breast cancer.