Proinflammatory cytokines, such as TNF-α, trigger phosphorylation and activation of the IKK complex, which is composed of two catalytic kinase subunits (IKK1 and IKK2) and the regulatory subunit NEMO. As a consequence, the inhibitory protein IκB is phosphorylated, ubiquitinated, and then degraded by the proteasome. The NF-κB dimer (e.g., p50 and p65) translocates into the nucleus and regulates target gene expression. Vlantis et al. overexpressed constitutively active IKK2 in IECs (6). This led to inflammation (immune cell infiltration) and tumorigenesis via intrinsic and paracrine mechanisms. As depicted here, they found that overexpression of constitutively active IKK2 led to activation of the Wnt/β-catenin pathway. However, it is not yet clear how this is regulated (directly via IKK or indirectly via NF-κB or NF-κB target genes).