ESR1 and breast cancer: In summary, we unraveled the inverse correlation between MOF and ERα in BC tissues and cells, and MOF overexpression promoted ERα protein degradation via CUL4B-mediated ubiquitin–proteasome pathway and HSP90 hyperacetylation that lead to the loss of chaperone binding of HSP90 with ERα, thus inhibiting transcriptional activation and cellular proliferation induced by estrogen and in vivo tumorigenicity of ERα+ BC cells.