研究者情報

ササキ　ヒデオ   SASAKI HIDEO   佐々木秀郎    所属   医学部医学科 腎泌尿器外科学    職種   客員教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Single-cell analysis reveals a preexisting drug-resistant subpopulation in the luminal breast cancer subtype.
掲載誌名	正式名：Cancer research 略　 称：Cancer Res ISSNコード：1538744500085472
掲載区分	国外
巻・号・頁	79(17),4412-4425頁
著者・共著者	Prieto-Vila Marta, Usuba Wataru, Takahashi Ryou-U, Shimomura Iwao, Sasaki Hideo, Ochiya Takahiro, Yamamoto Yusuke
発行年月	2019/09
概要	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.
DOI	10.1158/0008-5472.CAN-19-0122
PMID	31289135