Tamoxifen is one of the most frequently used endocrine medications for the treatment of estrogen receptor‐positive (ER + ) breast cancer (BC). Unfortunately, tamoxifen resistance (TR) brings more challenges to the clinical… Click to show full abstract
Tamoxifen is one of the most frequently used endocrine medications for the treatment of estrogen receptor‐positive (ER + ) breast cancer (BC). Unfortunately, tamoxifen resistance (TR) brings more challenges to the clinical treatment, and the mechanisms of TR have not yet been fully clarified. HGF/c‐Met is closely associated with cancer metastasis, but whether it is involved in TR remains unclear. In our study, we found that the activation of HGF/c‐Met was crucial for TR maintenance. Synergistic interaction with HOTAIR and EZH2 accelerated HGF expression by repressing miR‐141/200a. Additionally, HGF/c‐Met activated NF‐κB, forming a positive feedback loop of EZH2/HOTAIR‐miR‐141/200a‐HGF/c‐Met‐NF‐κB. Our findings indicated that HGF/c‐Met functioned as an important biomarker for TR, and HGF/c‐Met inhibition provided a novel approach to TR treatment.