Inflammation Meets Cancer, with NF-κB As the Matchmaker

Overview

Journal Nat Immunol

Date 2011 Jul 21

PMID 21772280

Citations 708

Authors

Yinon Ben-Neriah

Michael Karin

Affiliations

Soon will be listed here.

Abstract

Inflammation is a fundamental protective response that sometimes goes awry and becomes a major cofactor in the pathogenesis of many chronic human diseases, including cancer. Here we review the evolutionary relationship and opposing functions of the transcription factor NF-κB in inflammation and cancer. Although it seems to fulfill a distinctly tumor-promoting role in many types of cancer, NF-κB has a confounding role in certain tumors. Understanding the activity and function of NF-κB in the context of tumorigenesis is critical for its successful taming, an important challenge for modern cancer biology.

Citing Articles

Correlation Between Periodontal Disease and Oral, Oropharyngeal, and Parapharyngeal Cancers.

Daily Z, Mohammed N, Mohammed S, Hussein H Clin Cosmet Investig Dent. 2025; 17:147-158.

PMID: 40027983 PMC: 11869753. DOI: 10.2147/CCIDE.S512557.

Inflammation, microbiota, and pancreatic cancer.

Chen X, Sun F, Wang X, Feng X, Aref A, Tian Y Cancer Cell Int. 2025; 25(1):62.

PMID: 39987122 PMC: 11847367. DOI: 10.1186/s12935-025-03673-6.

The Role of Pomegranate () in Cancer Prevention and Treatment: Modulating Signaling Pathways From Inflammation to Metastasis.

Rauf A, Olatunde A, Akram Z, Hemeg H, Aljohani A, Al Abdulmonem W Food Sci Nutr. 2025; 13(2):e4674.

PMID: 39898127 PMC: 11782917. DOI: 10.1002/fsn3.4674.

The Mechanism of Acupuncture Therapy for Migraine: A Systematic Review of Animal Studies on Rats.

An Y, Zhang J, Ren Q, Liu J, Liu Z, Cao K J Pain Res. 2025; 18:473-487.

PMID: 39882184 PMC: 11776926. DOI: 10.2147/JPR.S504892.

iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer.

Del Moral-Martinez M, Sanchez-Uceta P, Clemente-Gonzalez R, Moreno-SanJuan S, Puentes-Pardo J, Khaldy H Biomolecules. 2025; 15(1).

PMID: 39858519 PMC: 11763104. DOI: 10.3390/biom15010125.

References

Foster S, Hargreaves D, Medzhitov R . Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature. 2007; 447(7147):972-8. DOI: 10.1038/nature05836. View

Neurath M, Pettersson S, Meyer zum Buschenfelde K, Strober W . Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Nat Med. 1996; 2(9):998-1004. DOI: 10.1038/nm0996-998. View

Bettermann K, Vucur M, Haybaeck J, Koppe C, Janssen J, Heymann F . TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer. Cancer Cell. 2010; 17(5):481-96. DOI: 10.1016/j.ccr.2010.03.021. View

Snapper C, Zelazowski P, Rosas F, Kehry M, Tian M, Baltimore D . B cells from p50/NF-kappa B knockout mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching. J Immunol. 1996; 156(1):183-91. View

Domazet-Loso T, Tautz D . Phylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa. BMC Biol. 2010; 8:66. PMC: 2880965. DOI: 10.1186/1741-7007-8-66. View

Greten F, Eckmann L, Greten T, Park J, Li Z, Egan L . IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004; 118(3):285-96. DOI: 10.1016/j.cell.2004.07.013. View

Lavon I, Pikarsky E, Gutkovich E, Goldberg I, Bar J, Oren M . Nuclear factor-kappaB protects the liver against genotoxic stress and functions independently of p53. Cancer Res. 2003; 63(1):25-30. View

Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D . Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A. 2009; 106(35):14978-83. PMC: 2736429. DOI: 10.1073/pnas.0809784106. View

WIEBECKE B, Brandts A, Eder M . Epithelial proliferation and morphogenesis of hyperplastic adenomatous and villous polyps of the human colon. Virchows Arch A Pathol Anat Histol. 1974; 364(1):35-49. DOI: 10.1007/BF01230856. View

10.

Duckett C . Apoptosis and NF-kappa B: the FADD connection. J Clin Invest. 2002; 109(5):579-80. PMC: 150897. DOI: 10.1172/JCI15197. View

11.

Rothwell P, Fowkes F, Belch J, Ogawa H, Warlow C, Meade T . Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2010; 377(9759):31-41. DOI: 10.1016/S0140-6736(10)62110-1. View

12.

Lawrence T, Gilroy D, Colville-Nash P, Willoughby D . Possible new role for NF-kappaB in the resolution of inflammation. Nat Med. 2001; 7(12):1291-7. DOI: 10.1038/nm1201-1291. View

13.

Squires D . NEOPLASIA IN A CORAL?. Science. 1965; 148(3669):503-5. DOI: 10.1126/science.148.3669.503. View

14.

Inokuchi S, Aoyama T, Miura K, Osterreicher C, Kodama Y, Miyai K . Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis. Proc Natl Acad Sci U S A. 2010; 107(2):844-9. PMC: 2818947. DOI: 10.1073/pnas.0909781107. View

15.

Keats J, Fonseca R, Chesi M, Schop R, Baker A, Chng W . Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell. 2007; 12(2):131-44. PMC: 2083698. DOI: 10.1016/j.ccr.2007.07.003. View

16.

Qian B, Pollard J . Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141(1):39-51. PMC: 4994190. DOI: 10.1016/j.cell.2010.03.014. View

17.

Dajee M, Lazarov M, Zhang J, Cai T, Green C, Russell A . NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature. 2003; 421(6923):639-43. DOI: 10.1038/nature01283. View

18.

Gillooly K, Pattoli M, Taylor T, Chen L, Cheng L, Gregor K . Periodic, partial inhibition of IkappaB Kinase beta-mediated signaling yields therapeutic benefit in preclinical models of rheumatoid arthritis. J Pharmacol Exp Ther. 2009; 331(2):349-60. DOI: 10.1124/jpet.109.156018. View

19.

Yang J, Liao X, Agarwal M, Barnes L, Auron P, Stark G . Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev. 2007; 21(11):1396-408. PMC: 1877751. DOI: 10.1101/gad.1553707. View

20.

Endo Y, Marusawa H, Chiba T . Involvement of activation-induced cytidine deaminase in the development of colitis-associated colorectal cancers. J Gastroenterol. 2010; 46 Suppl 1:6-10. DOI: 10.1007/s00535-010-0326-1. View