IKK and IKK-related kinases induce the phosphorylation of their downstream substrates, leading to their activation (yellow) or inhibition (orange). Regulation of these substrates by IKKα, IKKβ, IKKε, and TBK1 has been shown to contribute to tumor development by increasing tumor angiogenesis and metastasis, promoting cell proliferation, and generating resistance to cell apoptosis. See text for a detailed description of downstream inhibitory or activation substrates of IKK and IKK-related kinases.