SBEM confers paclitaxel resistance in breast cancer via DUSP16-mediated MAPK/AMPK pathway activation.

Small breast epithelial mucin (SBEM) is upregulated in primary breast tumors and metastatic lymph nodes and has been implicated in chemoresistance. While it has been identified as a potential biomarker for monitoring hematogenous micrometastasis in patients with breast cancer undergoing adjuvant chemotherapy, the molecular mechanisms by which SBEM confers this resistance remain unclear. Therefore, the present study aimed to elucidate the mechanisms by which SBEM regulates paclitaxel (PTX) resistance in breast cancer. To this aim, breast cancer cell lines with SBEM overexpression and knockdown were developed from parental drug-resistant strains. Additionally, AMPK activator 13 was used to investigate the involvement of the AMPK pathway in the SBEM-mediated effects. The results indicated that SBEM overexpression promoted cell viability and enhanced resistance to PTX in breast cancer cells. Conversely, SBEM knockdown significantly increased apoptosis, with a three-fold increase compared with the controls, and restored PTX sensitivity in drug-resistant cells. Mechanistically, SBEM was found to interact with dual-specificity phosphatase 16 (DUSP16) and upregulate its expression. Additionally, SBEM downregulation inhibited AMPK signaling activity, thereby suppressing cancer cell viability. In conclusion, abnormal activation of the AMPK signaling pathway was shown to contribute to PTX resistance in breast cancer. SBEM enhanced DUSP16 expression and activated the AMPK signaling pathway, thereby conferring resistance to PTX.