In summary, we discovered a pro-inflammatory function of DCLK1 in driving CRC aggressiveness via the XRCC5/COX2/PGE2 axis, which broadens the importance of DCLK1 in CRC pathogenesis, thus supporting the development of additional DCLK1 inhibitors for CRC treatment. The gene discussed is DCLK1; the disease is colorectal carcinoma.