期刊
CANCER RESEARCH
卷 79, 期 17, 页码 4412-4425出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-19-0122
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资金
- JSPS KAKENHI [19K16761, 17H04991]
- Japan Agency for Medical Research and Development (AMED)
- Grants-in-Aid for Scientific Research [17H04991, 19K16761] Funding Source: KAKEN
Drug resistance is a major obstacle in the treatment of breast cancer. Surviving cells lead to tumor recurrence and metastasis, which remains the main cause of cancer-related mortality. Breast cancer is also highly heterogeneous, which hinders the identification of individual cells with the capacity to survive anticancer treatment. To address this, we performed extensive single-cell gene-expression profiling of the luminal-type breast cancer cell line MCF7 and its derivatives, including docetaxel-resistant cells. Upregulation of epithelial-to-mesenchymal transition and stemness-related genes and downregulation of cell-cycle-related genes, which were mainly regulated by LEF1, were observed in the drug-resistant cells. Interestingly, a small number of cells in the parental population exhibited a gene-expression profile similar to that of the drug-resistant cells, indicating that the untreated parental cells already contained a rare subpopulation of stem-like cells with an inherent predisposition toward docetaxel resistance. Our data suggest that during chemotherapy, this population may be positively selected, leading to treatment failure. Significance: This study highlights the role of breast cancer intratumor heterogeneity in drug resistance at a single-cell level.
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