Cancer Letters
Volume 206, Issue 2 , Pages 193-199 , 8 April 2004

The IKK/NF-κB activation pathway—a target for prevention and treatment of cancer

Received 25 July 2003 ,Accepted 14 August 2003.

References 

  1. Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 1998;16:225–260
  2. Gilmore TD. Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel. Oncogene. 1999;18:6925–6937
  3. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002;109(Suppl):S81–S96
  4. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu. Rev. Immunol. 2000;18:621–663
  5. Li ZW, Chu W, Hu Y, Delhase M, Deerinck T, Ellisman M, et al.  The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis. J. Exp. Med. 1999;189:1839–1845
  6. Solan NJ, Miyoshi H, Carmona EM, Bren GD, Paya CV. RelB cellular regulation and transcriptional activity are regulated by p100. J. Biol. Chem. 2002;277:1405–1418
  7. Senftleben U, Cao Y, Xiao G, Greten FR, Krahn G, Bonizzi G, et al.  Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 2001;293:1495–1499
  8. Gilmore T, Gapuzan ME, Kalaitzidis D, Starczynowski D. Rel/NF-kappa B/I kappa B signal transduction in the generation and treatment of human cancer. Cancer Lett. 2002;181:1–9
  9. Xiao G, Cvijic ME, Fong A, Harhaj EW, Uhlik MT, Waterfield M, et al. Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha. Eur. Mol. Biol. Org. J. 2001;20:6805–6815
  10. Mosialos G. The role of Rel/NF-kappa B proteins in viral oncogenesis and the regulation of viral transcription. Semin. Cancer Biol. 1997;8:121–129
  11. Finco TS, Westwick JK, Norris JL, Beg AA, Der CJ, Baldwin AS. Oncogenic Ha-Ras-induced signaling activates NF-kappaB transcriptional activity, which is required for cellular transformation. J. Biol. Chem. 1997;272:24113–24116
  12. Reuther JY, Reuther GW, Cortez D, Pendergast AM, Baldwin AS. A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation. Genes Dev. 1998;12:968–981
  13. Perona R, Montaner S, Saniger L, Sanchez-Perez I, Bravo R, Lacal JC. Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins. Genes Dev. 1997;11:463–475
  14. Montaner S, Perona R, Saniger L, Lacal JC. Multiple signalling pathways lead to the activation of the nuclear factor kappaB by the Rho family of GTPases. J. Biol. Chem. 1998;273:12779–12785
  15. Karin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer. 2002;2:301–310
  16. 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;19:2690–2698
  17. Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin AS. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell. Biol. 1999;19:5785–5799
  18. Romashkova JA, Makarov SS. NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature. 1999;401:86–90
  19. Toth CR, Hostutler RF, Baldwin AS, Bender TP. Members of the nuclear factor kappa B family transactivate the murine c-myb gene. J. Biol. Chem. 1995;270:7661–7671
  20. Duyao MP, Kessler DJ, Spicer DB, Bartholomew C, Cleveland JL, Siekevitz M, et al. Transactivation of the c-myc promoter by human T cell leukemia virus type 1 tax is mediated by NF kappa B. J. Biol. Chem. 1992;267:16288–16291
  21. Perkins ND, Felzien LK, Betts JC, Leung K, Beach DH, Nabel GJ. Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300 coactivator. Science. 1997;275:523–527
  22. Wolff B, Naumann M. INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB. Oncogene. 1999;18:2663–2666
  23. Yu Q, Geng Y, Sicinski P. Specific protection against breast cancers by cyclin D1 ablation. Nature. 2001;411:1017–1021
  24. Cao Y, Bonizzi G, Seagroves TN, Greten FR, Johnson R, Schmidt EV, et al. IKKalpha provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell. 2001;107:763–775
  25. Karin M, Lin A. NF-kappaB at the crossroads of life and death. Nat. Immunol. 2002;3:221–227
  26. Thisse C, Perrin-Schmitt F, Stoetzel C, Thisse B. Sequence-specific transactivation of the Drosophila twist gene by the dorsal gene product. Cell. 1991;65:1191–1201
  27. Tergaonkar V, Pando M, Vafa O, Wahl G, Verma I. p53 Stabilization is decreased upon NFkappaB activation: a role for NFkappaB in acquisition of resistance to chemotherapy. Cancer Cell. 2002;1:493–503
  28. Zhou G, Kuo MT. NF-kappaB-mediated induction of mdr1b expression by insulin in rat hepatoma cells. J. Biol. Chem. 1997;272:15174–15183
  29. Bentires-Alj M, Barbu V, Fillet M, Chariot A, Relic B, Jacobs N, et al.  NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells. Oncogene. 2003;22:90–97
  30. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 1999;18:6853–6866
  31. Li N, Karin M. Ionizing radiation and short wavelength UV activate NF-kappaB through two distinct mechanisms. Proc. Natl. Acad. Sci. USA. 1998;95:13012–13017
  32. Wang CY, Mayo MW, Baldwin AS. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996;274:784–787
  33. Wang CY, Cusack JC, Liu R, Baldwin AS. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat. Med. 1999;5:412–417
  34. Cusack JC, Liu R, Baldwin AS. Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothe cin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation. Cancer Res. 2000;60:2323–2330
  35. Jones DR, Broad RM, Madrid LV, Baldwin AS, Mayo MW. Inhibition of NF-kappaB sensitizes non-small cell lung cancer cells to chemotherapy-induced apoptosis. Ann. Thorac. Surg. 2000;70:930–936 discussion 936–937
  36. Arlt A, Vorndamm J, Breitenbroich M, Folsch UR, Kalthoff H, Schmidt WE, et al. Inhibition of NF-kappaB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin. Oncogene. 2001;20:859–868
  37. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J. Clin. Invest. 2001;107:241–246
  38. Chilov D, Kukk E, Taira S, Jeltsch M, Kaukonen J, Palotie A, et al.  Genomic organization of human and mouse genes for vascular endothelial growth factor C. J. Biol. Chem. 1997;272:25176–25183
  39. Li X, Massa PE, Hanidu A, Peet GW, Aro P, Savitt A, et al.  IKKalpha, IKKbeta, and NEMO/IKKgamma are each required for the NF-kappa B-mediated inflammatory response program. J. Biol. Chem. 2002;277:45129–45140
  40. Takeshita H, Yoshizaki T, Miller WE, Sato H, Furukawa M, Pagano JS, et al. Matrix metalloproteinase 9 expression is induced by Epstein-Barr virus latent membrane protein 1 C-terminal activation regions 1 and 2. J. Virol. 1999;73:5548–5555
  41. Bond M, Baker AH, Newby AC. Nuclear factor kappaB activity is essential for matrix metalloproteinase-1 and -3 upregulation in rabbit dermal fibroblasts. Biochem. Biophys. Res. Commun. 1999;264:561–567
  42. Andela VB, Schwarz EM, Puzas JE, O'Keefe RJ, Rosier RN. Tumor metastasis and the reciprocal regulation of prometastatic and antimetastatic factors by nuclear factor kappaB. Cancer Res. 2000;60:6557–6562
  43. Johnson JP. Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev. 1999;18:345–357
  44. Forman HJ, Torres M. Redox signaling in macrophages. Mol. Aspects Med. 2001;22:189–216
  45. Peek RM, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat. Rev. Cancer. 2002;2:28–37
  46. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al.  Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature. 2000;404:398–402
  47. Keates S, Hitti YS, Upton M, Kelly CP. Helicobacter pylori infection activates NF-kappa B in gastric epithelial cells. Gastroenterology. 1997;113:1099–1109
  48. Kim H, Lim JW, Kim KH. Helicobacter pylori-induced expression of interleukin-8 and cyclooxygenase-2 in AGS gastric epithelial cells: mediation by nuclear factor-kappaB. Scand. J. Gastroenterol. 2001;36:706–716
  49. Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 1997;336:1066–1071
  50. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn's disease with colonic involvement. Lancet. 1990;336:357–359
  51. Neurath MF, Pettersson S, Meyer zum Buschenfelde KH, 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;2:998–1004
  52. Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, et al.  Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology. 1998;115:357–369
  53. Ardite E, Panes J, Miranda M, Salas A, Elizalde JI, Sans M, et al.  Effects of steroid treatment on activation of nuclear factor kappaB in patients with inflammatory bowel disease. Br. J. Pharmacol. 1998;124:431–433
  54. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75:263–274
  55. Berg DJ, Davidson N, Kuhn R, Muller W, Menon S, Holland G, et al.  Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J. Clin. Invest. 1996;98:1010–1020
  56. Bharti AC, Aggarwal BB. Chemopreventive agents induce suppression of nuclear factor-kappaB leading to chemosensitization. Ann. N. Y. Acad. Sci. 2002;973:392–395
  57. Wahl C, Liptay S, Adler G, Schmid RM. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J. Clin. Invest. 1998;101:1163–1174
  58. Weber CK, Liptay S, Wirth T, Adler G, Schmid RM. Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology. 2000;119:1209–1218
  59. Egan LJ, Mays DC, Huntoon CJ, Bell MP, Pike MG, Sandborn WJ, et al.  Inhibition of interleukin-1-stimulated NF-kappaB RelA/p65 phosphorylation by mesalamine is accompanied by decreased transcriptional activity. J. Biol. Chem. 1999;274:26448–26453
  60. Majumdar S, Aggarwal BB. Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation. J. Immunol. 2001;167:2911–2920
  61. Farrow DC, Vaughan TL, Hansten PD, Stanford JL, Risch HA, Gammon MD, et al.  Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol. Biomarkers Prev. 1998;7:97–102
  62. Zaridze D, Borisova E, Maximovitch D, Chkhikvadze V. Aspirin protects against gastric cancer: results of a case-control study from Moscow, Russia. Int. J. Cancer. 1999;82:473–476
  63. Yin MJ, Yamamoto Y, Gaynor RB. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature. 1998;396:77–80
  64. Yamamoto Y, Yin MJ, Lin KM, Gaynor RB. Sulindac inhibits activation of the NF-kappaB pathway. J. Biol. Chem. 1999;274:27307–27314
  65. Adams J. Proteasome inhibition: a novel approach to cancer therapy. Trends Mol. Med. 2002;8:S49–S54
  66. Amit S, Ben-Neriah Y. NF-kappaB activation in cancer: a challenge for ubiquitination- and proteasome-based therapeutic approach. Semin. Cancer Biol. 2003;13:15–28
  67. Adams J. Proteasome inhibition in cancer: development of PS-341. Semin. Oncol. 2001;28:613–619
  68. Haefner B. NF-kappaB: arresting a major culprit in cancer. Drug Discov. Today. 2002;7:653–663

PII: S0304-3835(03)00629-3

doi: 10.1016/j.canlet.2003.08.029

Cancer Letters
Volume 206, Issue 2 , Pages 193-199 , 8 April 2004