Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
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Gupta-2009-Identification of Se.pdf
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Author(s)
Jiang, Guozhi
Tao, Kai
Kuperwasser, Charlotte
Gupta, Piyush
Onder, Tamer T
Weinberg, Robert A
Lander, Eric Steven
Date Issued
August 2009
Journal
Cell
Publisher
Elsevier
Citation
Gupta, Piyush B., Tamer T. Onder, Guozhi Jiang, Kai Tao, Charlotte Kuperwasser, Robert A. Weinberg, and Eric S. Lander. “Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening.” Cell 138, no. 4 (August 2009): 645–659. © 2009 Elsevier Inc.
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Final published version
Abstract
Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2009.06.034
