Role, molecular mechanism and the potential target of breast cancer stem cells in breast cancer development.

Breast cancer (BC) is one of the most common malignant tumors in women globally, and its occurrence has surpassed lung cancer and become the biggest threat for women. At present, breast cancer treatment includes surgical resection or postoperative chemotherapy and radiotherapy. However, tumor relapse and metastasis usually lead to current therapy failure thanks to breast cancer stem cells (BCSCs)-mediated tumorigenicity and drug resistance. Drug resistance is mainly due to the long-term quiescent G0 phase, strong DNA repairability, and high expression of ABC transporter, and the tumorigenicity is reflected in the activation of various proliferation pathways related to BCSCs. Therefore, understanding the characteristics of BCSCs and their intracellular and extracellular molecular mechanisms is crucial for the development of targeted drugs for BCSCs. To this end, we discussed the latest developments in BCSCs research, focusing on the analysis of specific markers, critical signaling pathways that maintain the stemness of BCSCs，such as NOTCH, Wnt/β-catenin, STAT3, Hedgehog, and Hippo-YAP signaling, immunomicroenviroment and summarizes targeting therapy strategies for stemness maintenance and differentiation, which provides a theoretical basis for further exploration of treating breast cancer and preventing relapse derived from BCSCs.