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

• Published in: Cancer research (Chicago, Ill.) Vol. 79; no. 17; pp. 4412 - 4425
• Main Authors: Prieto-Vila, Marta, Usuba, Wataru, Takahashi, Ryou-U, Shimomura, Iwao, Sasaki, Hideo, Ochiya, Takahiro, Yamamoto, Yusuke
• Format: Journal Article
• Language: English
• Published: United States 01-09-2019
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-19-0122

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.