NF-kappaB and Cancer: How Intimate is This Relationship

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2009 Oct 14

PMID 19823771

Citations 188

Authors

Sahdeo Prasad

Jayaraj Ravindran

Bharat B Aggarwal

Affiliations

Soon will be listed here.

Abstract

NF-kappaB, a transcription factor first discovered in 1986, is now known to be closely connected to the process of tumorogenesis based on a multiplicity of evidence. (1) NF-kappaB is activated in response to tobacco, stress, dietary agents, obesity, alcohol, infectious agents, irradiation, and environmental stimuli that account for as much as 95% of all cancers. (2) The transcription factor has been linked with transformation of cells. (3) It is constitutively active in most tumor cells. (4) It has also been linked with the survival of cancer stem cells, an early progenitor cell that has acquired self-renewal potential. (5) NF-kappaB regulates the expression of most anti-apoptotic gene products associated with the survival of the tumor. (6) It also regulates the gene products linked with proliferation of tumors. (7) The transcription factor controls the expression of gene products linked with invasion, angiogenesis, and metastasis of cancer. (8) While most carcinogens activate NF-kappaB, most chemopreventive agents suppress its activation. These observations suggest that NF-kappaB is intimately intertwined with cancer growth and metastasis. The mechanism that leads to constitutive activation of NF-kappaB in hematological, gastrointestinal, genitourinary, gynecological, thoracic head and neck, breast, and skin cancers, and the ways NF-kappaB is activated are the topics of discussion in this review.

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References

Pacheco M, Nishimoto I, Mourao Neto M, Mantovani E, Brentani M . Prognostic significance of the combined expression of matrix metalloproteinase-9, urokinase type plasminogen activator and its receptor in breast cancer as measured by Northern blot analysis. Int J Biol Markers. 2001; 16(1):62-8. DOI: 10.1177/172460080101600109. View

Rabi T, Shukla S, Gupta S . Betulinic acid suppresses constitutive and TNFalpha-induced NF-kappaB activation and induces apoptosis in human prostate carcinoma PC-3 cells. Mol Carcinog. 2008; 47(12):964-73. PMC: 2864721. DOI: 10.1002/mc.20447. View

Bloor S, Ryzhakov G, Wagner S, Butler P, Smith D, Krumbach R . Signal processing by its coil zipper domain activates IKK gamma. Proc Natl Acad Sci U S A. 2008; 105(4):1279-84. PMC: 2234129. DOI: 10.1073/pnas.0706552105. View

Ban J, Yuk D, Woo K, Kim T, Lee U, Jeong H . Inhibition of cell growth and induction of apoptosis via inactivation of NF-kappaB by a sulfurcompound isolated from garlic in human colon cancer cells. J Pharmacol Sci. 2007; 104(4):374-83. DOI: 10.1254/jphs.fp0070789. View

Rowe H, Lopes L, Brown N, Efklidou S, Smallie T, Karrar S . Expression of vFLIP in a lentiviral vaccine vector activates NF-{kappa}B, matures dendritic cells, and increases CD8+ T-cell responses. J Virol. 2008; 83(4):1555-62. PMC: 2643792. DOI: 10.1128/JVI.00709-08. View

Schneider A, Martin-Villalba A, Weih F, Vogel J, Wirth T, Schwaninger M . NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat Med. 1999; 5(5):554-9. DOI: 10.1038/8432. View

Hinz M, Krappmann D, Eichten A, Heder A, Scheidereit C, Strauss M . NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. Mol Cell Biol. 1999; 19(4):2690-8. PMC: 84062. DOI: 10.1128/MCB.19.4.2690. View

Grosjean-Raillard J, Ades L, Boehrer S, Tailler M, Fabre C, Braun T . Flt3 receptor inhibition reduces constitutive NFkappaB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia. Apoptosis. 2008; 13(9):1148-61. DOI: 10.1007/s10495-008-0243-4. View

Park B, Zhang H, Zeng Q, Dai J, Keller E, Giordano T . NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF. Nat Med. 2006; 13(1):62-9. DOI: 10.1038/nm1519. View

10.

Ahn K, Sethi G, Aggarwal B . Embelin, an inhibitor of X chromosome-linked inhibitor-of-apoptosis protein, blocks nuclear factor-kappaB (NF-kappaB) signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Mol Pharmacol. 2006; 71(1):209-19. DOI: 10.1124/mol.106.028787. View

11.

Sandur S, Ichikawa H, Sethi G, Ahn K, Aggarwal B . Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and.... J Biol Chem. 2006; 281(25):17023-17033. DOI: 10.1074/jbc.M601595200. View

12.

Dumont A, Hehner S, Hofmann T, Ueffing M, Droge W, Schmitz M . Hydrogen peroxide-induced apoptosis is CD95-independent, requires the release of mitochondria-derived reactive oxygen species and the activation of NF-kappaB. Oncogene. 1999; 18(3):747-57. DOI: 10.1038/sj.onc.1202325. View

13.

Santos S, Monni R, Bouchaert I, Bernard O, Gisselbrecht S, Gouilleux F . Involvement of the NF-kappaB pathway in the transforming properties of the TEL-Jak2 leukemogenic fusion protein. FEBS Lett. 2001; 497(2-3):148-52. DOI: 10.1016/s0014-5793(01)02452-8. View

14.

Ravi R, Mookerjee B, van Hensbergen Y, Bedi G, Giordano A, El-Deiry W . p53-mediated repression of nuclear factor-kappaB RelA via the transcriptional integrator p300. Cancer Res. 1998; 58(20):4531-6. View

15.

BESANCON F, Atfi A, Gespach C, Cayre Y, Bourgeade M . Evidence for a role of NF-kappaB in the survival of hematopoietic cells mediated by interleukin 3 and the oncogenic TEL/platelet-derived growth factor receptor beta fusion protein. Proc Natl Acad Sci U S A. 1998; 95(14):8081-6. PMC: 20932. DOI: 10.1073/pnas.95.14.8081. View

16.

Brauns T, Schultewolter T, Dissemond J, Maschke J, Goos M . C-KIT expression in primary cutaneous T-cell lymphomas. J Cutan Pathol. 2004; 31(9):577-82. DOI: 10.1111/j.0303-6987.2004.00182.x. View

17.

Whitehead Jr R, Sugawara O, Maronpot R, Gladen B, Barrett J . Detection of multiple tumor suppressor genes for Syrian hamster fibrosarcomas by somatic cell hybridization. Somat Cell Mol Genet. 1992; 18(2):131-42. DOI: 10.1007/BF01233160. View

18.

Rettig M, Heber D, An J, Seeram N, Rao J, Liu H . Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism. Mol Cancer Ther. 2008; 7(9):2662-71. PMC: 2858627. DOI: 10.1158/1535-7163.MCT-08-0136. View

19.

Wu L, Pu Z, Feng J, Li G, Zheng Z, Shen W . The ubiquitin-proteasome pathway and enhanced activity of NF-kappaB in gastric carcinoma. J Surg Oncol. 2008; 97(5):439-44. DOI: 10.1002/jso.20952. View

20.

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