ERá, a critical transcriptional factor for breast cancer proliferation, is regulated by a complex binding repertoire that includes coactivators and corepressors. Here, we identified a novel class of ERá coregulator called CAC1. The CoRNR box of CAC1 was required for the binding to and inactivation of ERá. CAC1 also associated with histone demethylase LSD1 and suppressed LSD1-enhanced ERá activity. CAC1 impaired recruitment of ERá and LSD1 to the ERá-responsive promoter, leading to greater H3K9me3 accumulation. This effect was reversed by CAC1 depletion. Finally, CAC1 increased paclitaxel-induced cell death in ERá-positive MCF7 cells, which are paclitaxel-resistant. Overall, our study provides the first evidence that CAC1, associated with LSD1, functions as an ERá corepressor, implicating a potential antitumor target in ERá-positive breast cancer.
Antineoplastic Agents Breast Neoplasms