Endogenous inhibitors of nuclear factor-κB, an opportunity for cancer control

Excessive and prolonged activation of nuclear factor-κB (NF-κB) has been linked to numerous human diseases, especially cancer, because of the elevated expression of genes encoding antiapoptotic proteins, cytokines, chemokines, cell adhesion molecules, and so on. Eukaryotic cells have developed multiple mechanisms to keep this ubiquitous transcription factor in check. In addition to the inhibitor of κB family proteins, a number of endogenous molecules that negatively regulate the activation or activity of NF-κB have been identified. These molecules include A20, CYLD, cyPG15-deoxy- Δ^12,14-prostaglandin J₂, Foxj1, Twist proteins, and β-arrestins. The extended list of these endogenous inhibitors of NF-κB may provide new opportunities for the development of novel strategies for the intervention of malignant transformation. The question to be asked is how NF-κB is sustained activated in a number of cancers in which so many antagonists are surrounded.