Escaping fates with open states

The ability of embrionyc stem cells to give rise to any cell type relies on a remodelling protein that maintains open chromatin. But the chromatin landscape of these cells maybe more complex than previously thought.

http://www.nature.com/nature/journal/v460/n7257/pdf/nature08212.pdf

Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening

Article

Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening

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Piyush B. Gupta^{1, 3, 7, ,} , Tamer T. Onder^{1, 2, 7}, Guozhi Jiang^{1, 3}, Kai Tao⁴, Charlotte Kuperwasser⁴, Robert A. Weinberg^{1, 2, 6, 8, ,} and Eric S. Lander^{1, 2, 3, 5, 8, ,}

Received 21 October 2008;

revised 18 February 2009;

accepted 12 June 2009.

Published online: August 13, 2009.

Available online 13 August 2009.

Summary

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.

Cell death Regulation by BH3-Only family proteins.

El volumen 27, suplemento 1, de la revista Oncogene, está dedicado a la familia de proteínas con sólo el dominio BH3.

http://www.nature.com/onc/journal/v27/n1s/index.html