Abstract
Activation of nuclear factor (NF)-κB, one of the most investigated transcription factors, has been found to control multiple cellular processes in cancer including inflammation, transformation, proliferation, angiogenesis, invasion, metastasis, chemoresistance and radioresistance. NF-κB is constitutively active in most tumor cells, and its suppression inhibits the growth of tumor cells, leading to the concept of ‘NF-κB addiction’ in cancer cells. Why NF-κB is constitutively and persistently active in cancer cells is not fully understood, but multiple mechanisms have been delineated including agents that activate NF-κB (such as viruses, viral proteins, bacteria and cytokines), signaling intermediates (such as mutant receptors, overexpression of kinases, mutant oncoproteins, degradation of IκBα, histone deacetylase, overexpression of transglutaminase and iNOS) and cross talk between NF-κB and other transcription factors (such as STAT3, HIF-1α, AP1, SP, p53, PPARγ, β-catenin, AR, GR and ER). As NF-κB is ‘pre-active’ in cancer cells through unrelated mechanisms, classic inhibitors of NF-κB (for example, bortezomib) are unlikely to mediate their anticancer effects through suppression of NF-κB. This review discusses multiple mechanisms of NF-κB activation and their regulation by multitargeted agents in contrast to monotargeted agents, thus ‘one size does not fit all’ cancers.
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Acknowledgements
We thank Tamara Locke for carefully editing the manuscript. Dr Aggarwal is the Ransom Horne, Jr, Professor of Cancer Research. This work was supported by a grant from the Clayton Foundation for Research (B.B.A.), a core grant from the National Institutes of Health (CA-16 672), a program project grant from National Institutes of Health (NIH CA-124787-01A2), and a grant from the Center for Targeted Therapy of MD Anderson Cancer Center. M.M.C. thanks the University of Delhi, Department of Science & Technology, India-PURSE grant Dean(R)/2010/1142 and MD Anderson Cancer Center for financial support.
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Chaturvedi, M., Sung, B., Yadav, V. et al. NF-κB addiction and its role in cancer: ‘one size does not fit all’. Oncogene 30, 1615–1630 (2011). https://doi.org/10.1038/onc.2010.566
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DOI: https://doi.org/10.1038/onc.2010.566
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