tnfsf13 upregulation confers chemotherapeutic resistance via triggering autophagy initiation in triple-negative breast cancer

Since chemotherapy is a main strategy to treat triple-negative breast cancer (tnbc) patients currently, identifying a biomarker to predict chemotherapeutic responses is urgently needed for patients to avoid suffering through unnecessary chemotherapeutic treatments. here, we found that the endogenous expression of tnfsf13 in a panel of tnbc cell lines highly correlates with paclitaxel (ptx) and doxorubicin ic50 concentrations. whereas knocking down tnfsf13 enhances ptx effectiveness in ptx-insensitive mda-mb231 cells, recombinant tnfsf13 (rectnfsf13) desensitizes ptx-sensitive hcc1806 cells to ptx treatment. moreover, kaplan-meier analysis revealed that higher tnfsf13 mrna expression significantly predicts an increased risk for cancer recurrence in estrogen receptor (er)-negative breast cancer patients receiving an anthracycline-based treatment. accordingly, immunohistochemistry experiments indicated that higher levels of tnfsf13 protein are detected in tnbc patients who do not respond to an anthracycline-based treatment. the in silico analysis and western blotting demonstrated that tnfsf13 expression inversely associates with the activity of the akt-mtor pathway, which acts as a negative regulator of autophagy activity. significantly, the pharmaceutical inhibition of autophagy activity restores the therapeutic effectiveness of ptx in tnfsf13-treated hcc1806 cells. these findings suggest that tnfsf13 can serve as a predictive biomarker for tnbc patients, who can use it to decide whether to receive chemotherapy.