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Review
. 2014 Mar;37(3):189-95.
doi: 10.14348/molcells.2014.2353. Epub 2014 Mar 3.

NF-κB in cellular senescence and cancer treatment

Hua Jing  1 , Soyoung Lee
Affiliations
Review

NF-κB in cellular senescence and cancer treatment

Hua Jing et al. Mol Cells. 2014 Mar.

Abstract

The NF-κB pathway transcriptionally controls a large set of target genes that play important roles in cell survival, inflammation, and immune responses. While many studies showed anti-tumorigenic and pro-survival role of NF-κB in cancer cells, recent findings postulate that NF-κB participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF-κB. In this review, we discuss implications of the NF-κB signaling pathway in cancer. Particularly, we emphasize the connection of NF-κB with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF-κB produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example.

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Figures

Fig. 1.
Fig. 1.
NF-κB signaling pathway and cancer related mutations. Only canonical (classical) pathway is shown. Extracellular stimuli transmitted though receptor complexes activate IKK via phosphorylation. Consequently, IKK phosphorylates IκB, leading to its dissociation from inactive NF-κB complex and ubiquitin-mediated proteasomal degradation. Freed from IκB, active NF-κB dimer translocates into the nucleus and induces the transcription of various target genes involved in multiple cellular pathways. Cancer-relevant mutations, indicated in orange boxes, can occur in all steps of NF-κB signaling cascade.
Fig. 2.
Fig. 2.
A model of how oncogenic network influences cancer treatment outcome. How two oncogenic moieties (NF-κB and bcl2) are connected in a network at diagnosis - a linear pathway in which NF-κB drives bcl2 expression reminiscent of ABC DLBCL, or in independent parallel pathways reminiscent of GCB DLBCL - influences the cellular outcome and sensitivity to treatment using conventional chemotherapy and/or novel NF-κB inhibitor.
See this image and copyright information in PMC

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