Abstract 974: Genome-wide analysis of estrogen receptor b binding sites: Implications for endogenous anti-metastatic activity in inflammatory breast cancer

Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor a (ERa) negativity. We previously explored the second ER subtype, (ERb) and reported expression in IBC tumors and its correlation with reduced metastasis in patients. We have also seen decreased metastasis of IBC tumors when ERb is expressed or activated by chemical agonists. In contrast, ablation of ERb in IBC cells increased migration and stimulated signaling pathways that activate Rho GTPases promoting actin reorganization. We have now mapped all ERb binding sites in IBC cells and by interrogating this information together with gene expression data we identified genomic targets that mediate its tumor repressive effects. Through a combined analysis of cells that express endogenous ERb and knockout cells engineered to re-express the receptor we have defined how a biologically relevant ERb interacts with the cancer cell genome to control metastatic signals in IBC. We reveal key binding motifs and cis-regulatory chromatin sites and associate target genes with clinical outcomes to strengthen the relevance of ERb signaling for the progression of IBC. Our findings thus offer an opportunity to better understand the mechanism of ERb action that is critical step in validating its tumor repressive role in breast cancer. Citation Format: Ilias V. Karagounis, Spyros Tastsoglou, Anna Karavangeli, Amit Maity, Artemis Chatzigeorgiou, Christoforos Thomas. Genome-wide analysis of estrogen receptor b binding sites: Implications for endogenous anti-metastatic activity in inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 974.