1. Prostaglandin E 2 Promotes Colon Cancer Cell Growth Through a G s -Axin-ß-Catenin Signaling Axis
- Author
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Maria Domenica Castellone, Bart O. Williams, Kirk M. Druey, Hidemi Teramoto, and J. Silvio Gutkind
- Subjects
GTPase-activating protein ,G protein ,Biology ,Dinoprostone ,Cell Line ,Regulator of G protein signaling ,Axin Protein ,Genes, Reporter ,GSK-3 ,Heterotrimeric G protein ,GTP-Binding Protein alpha Subunits, Gs ,Humans ,Receptors, Prostaglandin E ,Protein kinase A ,Protein kinase B ,beta Catenin ,Cell Proliferation ,Multidisciplinary ,Receptors, Prostaglandin E, EP2 Subtype ,Cyclic AMP-Dependent Protein Kinases ,Repressor Proteins ,Colonic Neoplasms ,Cancer research ,cAMP-dependent pathway ,RGS Proteins ,Signal Transduction - Abstract
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 βγ subunits and the direct association of the G protein α s subunit with the regulator of G protein signaling (RGS) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3β from its complex with axin, thereby relieving the inhibitory phosphorylation of β-catenin and activating its signaling pathway. These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer.
- Published
- 2005
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