癌症干细胞推动肿瘤的发起、侵袭、转移和复发。在本研究中，我们评估了ERRα在维持乳腺癌干细胞（BCSCs）中的作用，使用乳腺癌细胞系。使用倒向激动剂XCT-790抑制ERRα，或在乳腺癌细胞中敲低ERRα，显著降低了乳球形体形成效率和乳球形体大小，以及CD44+/CD24-的BCSCs显著减少。XCT-790处理显著降低了MCF7和MDA-MB-231乳球形体形成干细胞中与干细胞维持相关的转录因子Oct4、Klf4、Sox2、Nanog和c-Myc的表达。此外，XCT-790导致乳球形体形成细胞的细胞周期停滞和凋亡。ERRα敲低或抑制下调了Notch1和β-连环蛋白的表达，而在MCF7细胞中过表达ERRα上调了这些蛋白的表达。此外，ERRα的抑制增强了紫杉醇抑制BCSCs的效力。这些结果表明ERRα对于BCSCs的维持至关重要，并暗示ERRα可能是乳腺癌治疗的潜在靶点。© 2023年作者（们），由Springer Nature旗下的Springer Science+Business Media, LLC独家许可使用。

Cancer stem cells drive tumor initiation, invasion, metastasis and recurrence. In the present study, we have evaluated the role of ERRα in the maintenance of breast cancer stem cells (BCSCs) using breast cancer cell lines. The inhibition of ERRα with the inverse agonist, XCT-790, or the knockdown of ERRα in breast cancer cells significantly reduced the mammosphere formation efficiency and mammosphere size along with a significant reduction in the CD44+/CD24- BCSCs. Treatment with XCT-790 significantly downregulated expression of the transcription factors involved in stem cell maintenance such as Oct4, Klf4, Sox2, Nanog and c-Myc in the mammosphere forming stem cells of MCF7 and MDA-MB-231. In addition, XCT-790 induced cell cycle arrest and apoptosis in the mammosphere-forming cells. The knockdown or inhibition of ERRα downregulated the expression of Notch1 and β-catenin, whereas the overexpression of ERRα in MCF7 cells upregulated the expression of these proteins. Moreover, the inhibition of ERRα synergistically enhanced the efficacy of paclitaxel in inhibiting the BCSCs. These results show that ERRα is crucial for the maintenance of BCSCs and suggest that ERRα could be a potential target for breast cancer treatment.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.