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Review
. 2016 Mar 29;5(2):15.
doi: 10.3390/cells5020015.

Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches

Mi Hee Park  1 , Jin Tae Hong  2
Affiliations
Review

Roles of NF-κB in Cancer and Inflammatory Diseases and Their Therapeutic Approaches

Mi Hee Park et al. Cells. .

Abstract

Nuclear factor-κB (NF-κB) is a transcription factor that plays a crucial role in various biological processes, including immune response, inflammation, cell growth and survival, and development. NF-κB is critical for human health, and aberrant NF-κB activation contributes to development of various autoimmune, inflammatory and malignant disorders including rheumatoid arthritis, atherosclerosis, inflammatory bowel diseases, multiple sclerosis and malignant tumors. Thus, inhibiting NF-κB signaling has potential therapeutic applications in cancer and inflammatory diseases.

Keywords: NF-κB; cancer; canonical pathway; inflammatory disease; non-canonical pathway; therapeutic approaches.

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Figures

Figure 1
Figure 1
The canonical NF-κB pathway (left) induced by signals including antigens, TLR ligands and cytokines such as TNF uses a wide variety of signaling adaptors to engage and activate the IKKβ subunit of the IKK complex. IKKβ phosphorylation of IκB proteins bound to NF-κB dimers results in ubiquitination (Ub) of IκB and proteasome-induced degradation. This allows NF-κB to enter the nucleus and be involved in controlling the transcription of gene encoding functions as diverse as inflammation, cell survival and cell division. The noncanonical pathway (right) engaged in by members of the TNF-like family of cytokines requires NIK to activate IKKα, which then phosphorylates p100 (NF-κB2), triggering its proteosomal processing needed for the activation of p52-RelB dimers. Among its functions, this specific NF-κB heterodimer controls gene expression crucial for lymphoid organogenesis.
Figure 2
Figure 2
NF-κB activation affects hallmarks of cancer and inflammatory diseases through the transcription of genes involved in cell proliferation, survival, angiogenesis, inflammation and tumor promotion and metastasis. BCL2, B-cell lymphoma protein 2; BCL-XL, also known as BCL2-like 1; BFL1, also known as BCL2A1; CDK2, cyclin-dependent kinase 2; COX2, cyclooxygenase 2; CXCL, chemokine (C-X-C motif) ligand; DR, death receptor; ELAM1, endothelial adhesion molecule 1; FLIP, also known as CASP8; GADD45beta, growth arrest and DNA-damage-inducible protein beta; HIF1alpha, hypoxia-inducible factor 1alpha; ICAM1, intracellular adhesion molecule 1; IEX-1L, radiation-inducible immediate early gene (also known as IER3); IL, interleukin; iNOS, inducible nitric oxide synthase; KAL1, Kallmann syndrome 1 sequence; MCP1, monocyte chemoattractant protein 1 (also known as CCL2); MIP2, macrophage inflammatory protein 2; MMP, matrix metalloproteinase; MnSOD, manganese superoxide dismutase (also known as SOD2); TNF, tumour necrosis factor; TRAF, TNF receptor-associated factor; uPA, urokinase plasminogen activator; VCAM1, vascular cell adhesion molecule 1; VEGF, vascular endothelial growth factor; XIAP, X-linked inhibitor of apoptosis protein.
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