ERα inhibits epithelial-mesenchymal transition by suppressing Bmi1 in breast cancer

In human breast cancer, estrogen receptor-alpha (ER alpha) suppresses epithelial-mesenchymal transition (EMT) and stemness, two crucial parameters for tumor metastasis; however, the underlying mechanism by which ERa regulates these two processes remains largely unknown. Bmi1, the polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog, regulates EMT transition, maintains the self-renewal capacity of stem cells, and is frequently overexpressed in human cancers. In the present study, ER alpha upregulated the expression of the epithelial marker, E-cadherin, in breast cancer cells through the transcriptional down-regulation of Bmi1. Furthermore, ER alpha overexpression suppressed the migration, invasion, and EMT of breast cancer cells. Notably, overexpression of ER alpha significantly decreased the CD44(high)/CD24(low) cell population and inhibited the capacity for mammosphere formation in ER alpha-negative breast cancer cells. In addition, overexpression of Bmi1 attenuated the ER alpha-mediated suppression of EMT and cell stemness. Immunohistochemistry revealed an inverse association of ER alpha and Bmi1 expression in human breast cancer tissue. Taken together, our findings suggest that ER alpha inhibits EMT and stemness through the downregulation of Bmi1.