Estrogen Receptor β-Mediated Inhibition of Actin-Based Cell Migration Suppresses Metastasis of Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma with high frequency of estrogen receptor a (ER alpha) negativity. Here we explored the role of the second ER subtype, ER beta, and report expression in IBC tumors and its correlation with reduced metastasis. Ablation of ER beta in IBC cells promoted cell migration and activated gene networks that control actin reorganization, including G-protein-coupled receptors and downstream effectors that activate Rho GTPases. Analysis of preclinical mouse models of IBC revealed decreased metastasis of IBC tumors when ER beta was expressed or activated by chemical agonists. Our findings support a tumor-suppressive role of ERb by demonstrating the ability of the receptor to inhibit dissemination of IBC cells and prevent metastasis. On the basis of these findings, we propose ER beta as a potentially novel biomarker and therapeutic target that can inhibit IBC metastasis and reduce its associated mortality. Significance: These findings demonstrate the capacity of ER beta to elicit antimetastatic effects in highly aggressive inflammatory breast cancer and propose ER beta and the identified associated genes as potential therapeutic targets in this disease.