Single-Cell Analysis Reveals a Preexisting Drug-Resistant Subpopulation in the Luminal Breast Cancer Subtype

Cancer Res. 2019 Sep 1;79(17):4412-4425. doi: 10.1158/0008-5472.CAN-19-0122. Epub 2019 Jul 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Caveolin 1 / genetics
  • Caveolin 2 / genetics
  • Cell Line, Tumor
  • Docetaxel / pharmacology
  • Drug Resistance, Neoplasm / genetics*
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoid Enhancer-Binding Factor 1 / genetics*
  • MCF-7 Cells
  • MicroRNAs / genetics
  • Neoplastic Stem Cells / pathology
  • Single-Cell Analysis / methods*
  • Vimentin / genetics
  • Wnt Signaling Pathway / genetics


  • Antineoplastic Agents
  • CAV1 protein, human
  • CAV2 protein, human
  • Caveolin 1
  • Caveolin 2
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • MIRN27 microRNA, human
  • MicroRNAs
  • VIM protein, human
  • Vimentin
  • Docetaxel