FIGURE 1

IKK-driven NF-B promotes the development of colitis-associated cancer (CAC) by acting in two different celltypes. NF-B activation in pre-malignant intestinal epithelial cells (IEC carrying oncogenic mutations induced by AOM exposure) results in upregulation of pro-survival genes such as Bcl-X_L, thereby preventing apoptotic elimination via genomic surveillance mechanisms. IKK-driven NF-B also contributes to CAC development in inflammatory cells (macrophages, dendritic cells and/or neutrophils of the lamina propria) where it induces expression of epithelial cell growth factors, such as IL-6.