NF-κB: tumor promoter or suppressor?

A role for the NF-κB family of transcription factors as tumor promoters is firmly established. However, other data suggest that NF-κB can also inhibit tumor growth. Moreover, NF-κB activity is modulated by tumor suppressors, such as p53 and ARF, whereby NF-κB subunits repress, rather than activate, the expression of tumor-promoting genes. This suggests a dual function of NF-κB during tumor progression – in the early stages, NF-κB inhibits tumor growth but, as further mutations lead to a loss of tumor suppressor expression, the oncogenic functions of NF-κB become unleashed, allowing it to actively contribute to tumorigenesis. Here, I discuss this hypothesis, its implications for NF-κB function, and how this might influence the use of NF-κB-based anticancer therapies.