Estrogen-related receptor alpha (ERRα) promotes the migration, invasion and angiogenesis of breast cancer stem cell-like cells

Breast cancer progression, metastasis and recurrence are largely driven by breast cancer stem cells (BCSCs), which constitute a subset of tumor cells exhibiting stem cell characteristics. In this study, we evaluated the role of estrogen-related receptor alpha (ERR alpha) in the migration, invasion and angiogenesis of BCSCs. The inhibition of ERR alpha using XCT790 or knockdown of ERR alpha using shRNA inhibited the mammosphere formation efficiency, as well as the migration and invasion of BCSCs derived from the mammospheres of MCF7 and MDA-MB-231 (MB231) cells. Conversely, the overexpression of ERR alpha significantly increased the migration and invasion of BCSCs derived from the mammosphere. In addition, the XCT790 treatment or shERR alpha significantly downregulated the epithelial-mesenchymal transition (EMT), as evidenced by the downregulation in the expression of vimentin, Snail, Slug and N-cadherin in the mammospheres of MCF7 and MB231 cells. The chorioallantoic membrane assay showed that the conditioned media from XCT790-treated and shERR alpha cells significantly inhibited blood vessel formation and vessel length. Furthermore, XCT790 treatment or shERR alpha also downregulated the expression of molecular markers of angiogenesis, such as VEGF-A and Ang-2 in the mammospheres. Conversely, the overexpression of ERR alpha in MCF7 cells significantly increased both EMT and angiogenesis. These findings suggest that ERR alpha inhibits the migration, invasion and angiogenesis of BCSCs, suggesting as a potential target for breast cancer therapy.