Gutkind et al.[239] first demonstrated that prostaglandin E2 (PGE2), the product of cyclooxygenase 2, enhances colon cancer progression by binding with the G protein-coupled receptor, EP2, by a signaling route that involves the activation of phosphoinositide-3-kinase (PI3K) and AKT/PKB, leading to the inactivation of Axin and release of GSK3β from its complex with Axin. The gene discussed is AKT1; the disease is malignant colon neoplasm.