Author/Authors :
Wang، نويسنده , , Dingzhi and Wang، نويسنده , , Haibin and Shi، نويسنده , , Qiong and Katkuri، نويسنده , , Sharada and Walhi، نويسنده , , Walter and Desvergne، نويسنده , , Beatrice and Das، نويسنده , , Sanjoy K. and Dey، نويسنده , , Sudhansu K. and DuBois، نويسنده , , Raymond N.، نويسنده ,
Abstract :
Cyclooxygenase-derived prostaglandin E2 (PGE2) 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 PGE2-induced intestinal carcinogenesis are unclear. Here we report that PGE2 indirectly transactivates PPARδ through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE2 treatment of Apcmin mice dramatically increased intestinal adenoma burden, which was negated in Apcmin 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.
