NF-κB Signaling in Neoplastic Transition from Epithelial to Mesenchymal Phenotype

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2023 Oct 18

PMID 37853467

Authors

Amy Oh

Makayla Pardo

Anaelena Rodriguez

Connie Yu

Lisa Nguyen

Olin Liang

Anna Chorzalska

Patrycja M Dubielecka

Affiliations

Soon will be listed here.

Abstract

NF-κB transcription factors are critical regulators of innate and adaptive immunity and major mediators of inflammatory signaling. The NF-κB signaling is dysregulated in a significant number of cancers and drives malignant transformation through maintenance of constitutive pro-survival signaling and downregulation of apoptosis. Overactive NF-κB signaling results in overexpression of pro-inflammatory cytokines, chemokines and/or growth factors leading to accumulation of proliferative signals together with activation of innate and select adaptive immune cells. This state of chronic inflammation is now thought to be linked to induction of malignant transformation, angiogenesis, metastasis, subversion of adaptive immunity, and therapy resistance. Moreover, accumulating evidence indicates the involvement of NF-κB signaling in induction and maintenance of invasive phenotypes linked to epithelial to mesenchymal transition (EMT) and metastasis. In this review we summarize reported links of NF-κB signaling to sequential steps of transition from epithelial to mesenchymal phenotypes. Understanding the involvement of NF-κB in EMT regulation may contribute to formulating optimized therapeutic strategies in cancer. Video Abstract.

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References

Fan Y, Mao R, Yang J . NF-κB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell. 2013; 4(3):176-85. PMC: 4875500. DOI: 10.1007/s13238-013-2084-3. View

Umezawa K . Inhibition of tumor growth by NF-kappaB inhibitors. Cancer Sci. 2006; 97(10):990-5. PMC: 11158475. DOI: 10.1111/j.1349-7006.2006.00285.x. View

Hoesel B, Schmid J . The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 2013; 12:86. PMC: 3750319. DOI: 10.1186/1476-4598-12-86. View

Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M . Guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2020; 21(6):341-352. PMC: 7250738. DOI: 10.1038/s41580-020-0237-9. View

Bao B, Thakur A, Li Y, Ahmad A, Azmi A, Banerjee S . The immunological contribution of NF-κB within the tumor microenvironment: a potential protective role of zinc as an anti-tumor agent. Biochim Biophys Acta. 2011; 1825(2):160-72. PMC: 3811120. DOI: 10.1016/j.bbcan.2011.11.002. View

Burley S . Rel revealed: cocrystal structures of the NF-kappa B p50 homodimer. Chem Biol. 1995; 2(2):77-81. DOI: 10.1016/1074-5521(95)90279-1. View

Gutierrez H, Davies A . Regulation of neural process growth, elaboration and structural plasticity by NF-κB. Trends Neurosci. 2011; 34(6):316-25. PMC: 3115056. DOI: 10.1016/j.tins.2011.03.001. View

Cramer P, Muller C . A firm hand on NFkappaB: structures of the IkappaBalpha-NFkappaB complex. Structure. 1999; 7(1):R1-6. DOI: 10.1016/s0969-2126(99)80002-1. View

Hacker H, Karin M . Is NF-kappaB2/p100 a direct activator of programmed cell death?. Cancer Cell. 2002; 2(6):431-3. DOI: 10.1016/s1535-6108(02)00213-1. View

10.

Hoffmann A, Natoli G, Ghosh G . Transcriptional regulation via the NF-kappaB signaling module. Oncogene. 2006; 25(51):6706-16. DOI: 10.1038/sj.onc.1209933. View

11.

Chen F, Ghosh G . Regulation of DNA binding by Rel/NF-kappaB transcription factors: structural views. Oncogene. 1999; 18(49):6845-52. DOI: 10.1038/sj.onc.1203224. View

12.

Huxford T, Ghosh G . A structural guide to proteins of the NF-kappaB signaling module. Cold Spring Harb Perspect Biol. 2010; 1(3):a000075. PMC: 2773632. DOI: 10.1101/cshperspect.a000075. View

13.

Ghosh G, Van Duyne G, Ghosh S, SIGLER P . Structure of NF-kappa B p50 homodimer bound to a kappa B site. Nature. 1995; 373(6512):303-10. DOI: 10.1038/373303a0. View

14.

Muller C, Rey F, Sodeoka M, Verdine G, Harrison S . Structure of the NF-kappa B p50 homodimer bound to DNA. Nature. 1995; 373(6512):311-7. DOI: 10.1038/373311a0. View

15.

Kuriyan J, Thanos D . Structure of the NF-kappa B transcription factor: a holistic interaction with DNA. Structure. 1995; 3(2):135-41. DOI: 10.1016/s0969-2126(01)00143-5. View

16.

Zheng C, Yin Q, Wu H . Structural studies of NF-κB signaling. Cell Res. 2010; 21(1):183-95. PMC: 3044936. DOI: 10.1038/cr.2010.171. View

17.

Gilmore T . Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006; 25(51):6680-4. DOI: 10.1038/sj.onc.1209954. View

18.

Napetschnig J, Wu H . Molecular basis of NF-κB signaling. Annu Rev Biophys. 2013; 42:443-68. PMC: 3678348. DOI: 10.1146/annurev-biophys-083012-130338. View

19.

Dyson H, Komives E . Role of disorder in IκB-NFκB interaction. IUBMB Life. 2012; 64(6):499-505. PMC: 3575514. DOI: 10.1002/iub.1044. View

20.

Hinz M, Scheidereit C . The IκB kinase complex in NF-κB regulation and beyond. EMBO Rep. 2013; 15(1):46-61. PMC: 4303448. DOI: 10.1002/embr.201337983. View