Prostaglandin E 2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor δ

Abstract

Cyclooxygenase-derived prostaglandin E 2 (PGE 2) is the predominant prostanoid found in most colorectal cancers (CRC) and is known to promote colon carcinoma growth and invasion. However, the key downstream signaling pathways necessary for PGE 2-induced intestinal carcinogenesis are unclear. Here we report that PGE 2 indirectly transactivates PPARδ through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE 2 treatment of Apc min mice dramatically increased intestinal adenoma burden, which was negated in Apc min mice lacking PPARδ. We demonstrate that PPARδ is a focal point of crosstalk between the prostaglandin and Wnt signaling pathways which results in a shift from cell death to cell survival, leading to increased tumor growth.