IKK/NF-κB signaling: balancing life and death – a new approach to cancer therapy
Jun-Li Luo, … , Hideaki Kamata, Michael Karin
Jun-Li Luo, … , Hideaki Kamata, Michael Karin
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2625-2632. https://doi.org/10.1172/JCI26322.
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Review Series

IKK/NF-κB signaling: balancing life and death – a new approach to cancer therapy

Abstract

IκB kinase/NF-κB (IKK/NF-κB) signaling pathways play critical roles in a variety of physiological and pathological processes. One function of NF-κB is promotion of cell survival through induction of target genes, whose products inhibit components of the apoptotic machinery in normal and cancerous cells. NF-κB can also prevent programmed necrosis by inducing genes encoding antioxidant proteins. Regardless of mechanism, many cancer cells, of either epithelial or hematopoietic origin, use NF-κB to achieve resistance to anticancer drugs, radiation, and death cytokines. Hence, inhibition of IKK-driven NF-κB activation offers a strategy for treatment of different malignancies and can convert inflammation-induced tumor growth to inflammation-induced tumor regression.

Authors

Jun-Li Luo, Hideaki Kamata, Michael Karin

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Control of cell survival and death through NF-κB–JNK cross-talk. Positiv...
Control of cell survival and death through NF-κB–JNK cross-talk. Positive feedback loops exist between ROS and caspases, caspases and JNK, and JNK and ROS. Negative feedback loops exist between NF-κB and caspases, and NF-κB and ROS. NF-κB functions as a pro-survival transcription factor by inducing the expression of antiapoptotic genes, such as the Bcl-2 family members and caspase inhibitors, and antioxidant genes, such as MnSOD and FHC. Activation of NF-κB also results in inhibition of prolonged JNK activation, mostly through inhibition of ROS accumulation. Inhibition of NF-κB enhances PCD, which can be either apoptotic or necrotic, by removing the negative feedback loops.