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Review
. 2017 May 25;5(2):26.
doi: 10.3390/biomedicines5020026.

NF-κB Members Left Home: NF-κB-Independent Roles in Cancer

Carlota Colomer  1 , Laura Marruecos  2 , Anna Vert  3 , Anna Bigas  4 , Lluis Espinosa  5
Affiliations
Review

NF-κB Members Left Home: NF-κB-Independent Roles in Cancer

Carlota Colomer et al. Biomedicines. .

Abstract

Nuclear factor-κB (NF-κB) has been long considered a master regulator of inflammation and immune responses. Additionally, aberrant NF-κB signaling has been linked with carcinogenesis in many types of cancer. In recent years, the study of NF-κB members in NF-κB unrelated pathways provided novel attractive targets for cancer therapy, specifically linked to particular pathologic responses. Here we review specific functions of IκB kinase complexes (IKKs) and IκBs, which have distinctly tumor promoting or suppressing activities in cancer. Understanding how these proteins are regulated in a tumor-related context will provide new opportunities for drug development.

Keywords: Cancer; IKKs; IκBs; NF-κB; Non-conventional pathways.

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Conflict of interest statement

The authors declare no conflicts of interests.

Figures

Figure 1
Figure 1
Pro-tumorigenic functions of the NF-κB members. In CRC, IKKα phosphorylates the nuclear co-repressors N-CoR and SMRT, inducing its dissociation from the chromatin. In prostate cancer cells IKKα regulates the gene transcription of the metastasis repressor Maspin. The proteolytic fragment p45-IKKα is activated by BRAF and TAK1 in the endosomal compartment, and upon activation can phosphorylate histone H3 and SMRT. Moreover, nuclear IKKα contributes to the chromatin release of IκBα, and stimulates the nuclear export of p27/Kip1, thereby supporting the proliferation and expansion of tumor cells. On the other hand, IKKβ phosphorylates FOXO3a, leading to its nuclear exclusion and protein degradation. Arrows: formula image Activation/Regulation/Phosphorylation; formula image Migration; formula image Inactivation.
Figure 2
Figure 2
Tumor-suppressing functions of IKKα and IκBα. On one hand, IKKα increases SMAD transcriptional activity and decreases EGF transcription. It also promotes G2/M phase progression by de-repressing 14-3-3σ gene expression through preventing DNA and histone methylation on its promoter. On the other hand, IκBα is bound to histones and nuclear co-repressors, such as PRC2 regulating the expression of genes related to development and differentiation. Arrows: formula image Activation/Regulation/Phosphorylation; formula image Inactivation; formula image Inhibition
See this image and copyright information in PMC

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