We first identified Stat3 as a novel downstream target of CRHR2/Ucn2 signaling in CRC, by demonstrating significant suppression of IL-6-mediated Stat3 (Tyr703) phosphorylation after CRHR2 induction and activation by Ucn2, followed by decreased cell proliferation in vitro and diminished tumor growth in vivo. Here, STAT3 is linked to colorectal carcinoma.