PGE2 also can activate multiple signaling cascades, including the MAPK, NF-κB, and PI3K/Akt pathways,(54–56) and recently, it has been reported to crosstalk with and activate the β-catenin signaling pathway, well known to play an important role in cell survival.(35) In colon cancer, PGE2 activates the EP2 receptor, leading to activation of PI3K and the protein kinase Akt by free G-protein βγ subunits and the direct association of the G-protein αs subunit with axin. This evidence concerns the gene AKT1 and malignant colon neoplasm.