Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice

Levels of SIGIRR are lower in human colorectal tumors, compared with nontumor tissues; tumors contain the dominant-negative isoform SIGIRRΔE8. This mutant protein blocks localization of full-length SIGIRR to the surface of colon epithelial cells and its ability to downregulate IL1R signaling. Expression of SIGIRRN86/102S in the colonic epithelium of mice increases expression of inflammatory cytokines and formation and size of colitis-associated tumors.