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.
Keywords: HGF/c‐Met; HOTAIR; miR‐141/200a; tamoxifen resistance.
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