IKK- and NF-κB-mediated functions in carcinogenesis.
Since the initial cloning of RelA and its close relationship to c-Rel, the cellular homolog of the viral oncoprotein v-Rel, the nuclear factor κB (NF-κB) signaling pathway and its upstream activating kinase complex (IκB-kinase) have been suspected to play a major role in tumorigenesis. This was further corroborated by the discovery of oncogenic mutations in NF-κB proteins in certain lymphoid malignancies and the notion that NF-κB is persistently activated in a large variety of solid tumors. With the advent of conditional knockout mice allowing tissue-specific targeting of the various components of the NF-κB signaling pathway, it was possible to genetically test the cell autonomous and non-autonomous functions of NF-κB in inflammation-associated cancer as well as sporadic cancers. Here, we review molecular evidence that demonstrates the various functions of NF-κB during different tumor stages and that supports the rationale to target NF-κB in cancer prevention and therapy.
Arkan
Melek C
MC
2nd Department of Medicine, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, 81675, Munich, Germany.
Greten
Florian R
FR
D000818:Animals; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D009369:Neoplasms / Q000209:etiology* / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000473:pathology; D015398:Signal Transduction
D016328:NF-kappa B; D051550:I-kappa B Kinase