cyclooxygenase-2 (COX-2) 与其 代谢产物前列腺素E2 (PGE2) 怎么促进结肠癌依然不清楚, Castellone 等现在揭示, PGE2 通过其受体EP2激活PI3K和蛋白激酶Akt, 并直接结合axin蛋白, 进而释放并钝化糖元合成激酶GSK3, 导致 catenin 去磷酸化和激活, 最终促进结肠癌细胞增殖。

Science 2 December 2005:Vol. 310. No. 5753, pp. 1504 - 1510

Prostaglandin E2 Promotes Colon Cancer Cell Growth Through a Gs-Axin-?-Catenin Signaling Axis Maria Domenica Castellone,1 Hidemi Teramoto,2 Bart O. Williams,3 Kirk M. Druey,4 J. Silvio Gutkind1* How cyclooxygenase-2 (COX-2) and its proinflammatory metabolite prostaglandin E2 (PGE2) enhance colon cancer progression remains poorly understood. We show that PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)–coupled receptor, EP2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase Akt by free G protein ? subunits and the direct association of the G protein s subunit with the regulator of G protein signaling (RGS) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3? from its complex with axin, thereby relieving the inhibitory phosphorylation of ?-catenin and activating its signaling pathway. These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer.