Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation.

BACKGROUND

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.