1. Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation
- Author
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Peter, Grudzien, Shelly, Lo, Kathy S, Albain, Patricia, Robinson, Prabha, Rajan, Peter R, Strack, Todd E, Golde, Lucio, Miele, and Kimberly E, Foreman
- Subjects
Receptors, Notch ,Receptor, ErbB-2 ,Cell Line, Tumor ,Spheroids, Cellular ,Thiadiazoles ,Neoplastic Stem Cells ,Humans ,Breast Neoplasms ,Female ,Amyloid Precursor Protein Secretases ,Cyclic S-Oxides ,Signal Transduction - Abstract
Cancer stem cells (CSCs) are believed to be responsible for breast cancer formation and recurrence; therefore, therapeutic strategies targeting CSCs must be developed. One approach may be targeting signaling pathways, like Notch, that are involved in stem cell self-renewal and survival.Breast cancer stem-like cells derived from cell lines and patient samples were examined for Notch expression and activation. The effect of Notch inhibition on sphere formation, proliferation, and colony formation was determined.Breast cancer stem-like cells consistently expressed elevated Notch activation compared with bulk tumor cells. Blockade of Notch signaling using pharmacologic and genomic approaches prevented sphere formation, proliferation, and/or colony formation in soft agar. Interestingly, a gamma-secretase inhibitor, MRK003, induced apoptosis in these cells.Our findings support a crucial role for Notch signaling in maintenance of breast cancer stem-like cells, and suggest Notch inhibition may have clinical benefits in targeting CSCs.
- Published
- 2010