IKK/NF-kappaB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis

Our understanding of the molecular mechanisms that link inflammation and cancer has significantly increased in recent years. Here, we analyse genetic evidence indicating that the transcription factors nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) have a central role in this context by regulating distinct functions in cancer cells and surrounding non-tumorigenic cells. In immune cells, NF-kappaB induces the transcription of genes that encode pro-inflammatory cytokines, which can act in a paracrine manner on initiated cells. By contrast, in tumorigenic cells, both NF-kappaB and STAT3 control apoptosis, and STAT3 can also enhance proliferation. Consequently, inflammation should be considered as a valuable target for cancer prevention and therapy.