PPAR Delta as a Therapeutic Target in Triple-Negative Breast Cancers

PPAR is a member of peroxisome proliferators activated receptors which play important role in regulating cellular metabolisms. Basal-like breast cancers accounting for 15 of all breast cancer cases tend to be very aggressive and have poor prognosis. Basal-like breast cancers are considered to be derived from mammary stem cells. Abnormal activation of Wnt signaling is often found in human basal-like breast cancers. Here we report that PPAR expression is induced by Wnt signaling in mammary stem cells. Activation of PPAR by its ligands and fatty acids promotes the proliferation of mammary stem cells. The proliferation of mammary cancer stem cells is stimulated by PPAR agonists. Activation of PPAR promotes while its inhibition suppresses the tumorigenesis of MMTV-Wnt1 transgenic mice. We also found that PPAR antagonist inhibits the proliferation and anchorage-independent growth of a human basal-like breast cancer cell line.