Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer*

Triple-negative breast cancers (TNBCs) are characterized by low overall survival and poor response to therapy because of their aggressiveness and limited available treatments. We found a subset of TNBC expressing the master regulator estrogen receptor beta (ERβ1) and characterized the effect of this nuclear receptor in human TNBC cells by a multiomics approach. Results highlight transcriptome deregulation by ERβ involving association with chromatin remodeling complexes, including PRC1/2, and provide an explanation for its oncosuppressive effects on TNBC cells.