CXCL10 mediates breast cancer tamoxifen resistance and promotes estrogen-dependent and independent proliferation.

Although 70% of estrogen receptor (ER)-positive breast cancer patients can benefit from tamoxifen therapy, the rapid development of tamoxifen resistance hampers the treatment advantage. In this investigation, we found that the serum level of CXCL10 in breast cancer patients was positively correlated with tumor size and ER status. Furthermore, GSE22220 dataset analysis demonstrated that CXCL10 expression in the tumor was correlated with tumor grade and lymphatic metastasis status, and Kaplan-Meier analysis indicated that patients with high CXCL10 expression had a poor prognosis. Estrogen-deprived MCF7 cells were transfected with CXCL10 luciferase reporter plasmid and treated with 10 nM estrogen. Luciferase reporter assay confirmed that CXCL10 was regulated by estrogen. CXCL10 promoted the proliferation of both parental MCF7 cells and tamoxifen-resistant (TamR) MCF7 cells through the AKT pathway, while CXCL10 inhibition restored the sensitivity of TamR cells to tamoxifen. All of these data indicate that CXCL10 could be utilized as a biomarker to predict the prognosis of breast cancer and as a therapeutic target to treat tamoxifen resistant cases.