These data indicate that TFF3 promotes PTGS2 expression and secondary PGE2 production and that PGE2, in turn, activates STAT3 and increases PTGS2 expression through PTGER4-cAMP-PKA-SRC signaling, suggesting a local feed-forward loop governing PTGS2 production in CRC cells exposed to TFF3. Here, PTGER4 is linked to colorectal carcinoma.