Breast Cancer Stem Cells: Biomarkers, Identification and Isolation Methods, Regulating Mechanisms, Cellular Origin, and Beyond

SIMPLE SUMMARY: Breast cancer stem cells are blamed to be responsible for breast cancer tumorigenesis, metastasis, drug resistance and tumor recurrence. Therefore, it is critical to identify this subset of cells and understand their molecular mechanisms for the development of breast cancer treatment strategies. Here, we review the recent advances in breast cancer stem cell studies in terms of available biomarkers, identification and isolation methods, molecular mechanisms, and methods for studying their cellular origin and lineage development. ABSTRACT: Despite recent advances in diagnosis and treatment, breast cancer (BC) is still a major cause of cancer-related mortality in women. Breast cancer stem cells (BCSCs) are a small but significant subpopulation of heterogeneous breast cancer cells demonstrating strong self-renewal and proliferation properties. Accumulating evidence has proved that BCSCs are the driving force behind BC tumor initiation, progression, metastasis, drug resistance, and recurrence. As a heterogeneous disease, BC contains a full spectrum of different BC subtypes, and different subtypes of BC further exhibit distinct subtypes and proportions of BCSCs, which correspond to different treatment responses and disease-specific outcomes. This review summarized the current knowledge of BCSC biomarkers and their clinical relevance, the methods for the identification and isolation of BCSCs, and the mechanisms regulating BCSCs. We also discussed the cellular origin of BCSCs and the current advances in single-cell lineage tracing and transcriptomics and their potential in identifying the origin and lineage development of BCSCs.