engleski

IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer

Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Proinflammatory cytokines have been suggested to regulate preneoplastic growth during CAC tumorigenesis. Interleukin 6 (IL-6) is a multifunctional NF-kappaB-regulated cytokine that acts on epithelial and immune cells. Using genetic tools, we now demonstrate that IL-6 is a critical tumor promoter during early CAC tumorigenesis. In addition to enhancing proliferation of tumor-initiating cells, IL-6 produced by lamina propria myeloid cells protects normal and premalignant intestinal epithelial cells (IECs) from apoptosis. The proliferative and survival effects of IL-6 are largely mediated by the transcription factor Stat3, whose IEC-specific ablation has profound impact on CAC tumorigenesis. Thus, the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs.

cellcycle; inflammatory-bowel-disease; Nf-kappa-b; Gp130 mutant mice; colon-cancer; mouse model; ulcerative-colitis; colorectal-cancer; Tgf-beta; bacterial pathogens; designer cytokine

Janoš Terzić, Sergei Grivennikov i Eliad Karin autori su s podijeljenim prvim autorstvom.