Prostaglandin E2 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.