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.
journal_name
Celljournal_title
Cellauthors
Gupta PB,Onder TT,Jiang G,Tao K,Kuperwasser C,Weinberg RA,Lander ESdoi
10.1016/j.cell.2009.06.034subject
Has Abstractpub_date
2009-08-21 00:00:00pages
645-659issue
4eissn
0092-8674issn
1097-4172pii
S0092-8674(09)00781-8journal_volume
138pub_type
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