C-Rel is a critical mediator of NF-?B-dependent TRAIL resistance of pancreatic cancer cells

Cell Death and Disease

Volumn 5, Issue 10, 2014, Pages

  Geismann, C ^a   Grohmann, F ^a   Sebens, S ^b   Wirths, G ^a   Dreher, A ^a   Hasler R ^a   Rosenstiel, P ^a   Hauser, C ^c   Egberts, J H ^c   Trauzold, A ^a   Schneider, G ^d   Sipos, B ^e   Zeissig, S ^a   Schreiber, S ^a   Schafer H ^a   Arlt, A ^a  

^a UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^b Institute for Experimental Medicine   (Germany)

^c Institute of Clinical Molecular Biology ^*  (Germany)

^d TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^e UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CASPASE 7; CELECOXIB; CYCLOOXYGENASE 2; DNA DIRECTED DNA POLYMERASE ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 8; MESSENGER RNA; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR REL; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; ANTINEOPLASTIC AGENT; NFATC2 PROTEIN, HUMAN; PTGS2 PROTEIN, HUMAN; TRANSCRIPTION FACTOR RELA;

APOPTOSIS; ARTICLE; BINDING AFFINITY; CANCER RESISTANCE; CELL CYCLE G1 PHASE; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DNA BINDING; DNA PROTEIN COMPLEX; ENZYME ACTIVITY; GENE EXPRESSION; GENE TARGETING; GENETIC ASSOCIATION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; PROMOTER REGION; TRANSCRIPTION INITIATION; WESTERN BLOTTING; CARCINOMA, PANCREATIC DUCTAL; DRUG RESISTANCE; GENETICS; METABOLISM; PANCREATIC NEOPLASMS; PATHOPHYSIOLOGY; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; CYCLOOXYGENASE 2; DRUG RESISTANCE, NEOPLASM; HUMANS; NF-KAPPA B; NFATC TRANSCRIPTION FACTORS; PANCREATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-REL; TNF-RELATED APOPTOSIS-INDUCING LIGAND; TRANSCRIPTION FACTOR RELA;

EID: 84927909384     PISSN: None     EISSN: 20414889     Source Type: Journal    
DOI: 10.1038/cddis.2014.417     Document Type: Article

References (65)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. Cancer J Clin 2013; 63: 11-30.
2. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-1825.
3. Hill R, Rabb M, Madureira PA, Clements D, Gujar SA, Waisman DM et al. Gemcitabinemediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy. Cell Death Dis 2013; 4: e791.
4. Arlt A, Muerkoster SS, Schafer H. Targeting apoptosis pathways in pancreatic cancer. Cancer Lett 2013; 332: 346-358.
5. Wormann SM, Diakopoulos KN, Lesina M, Algul H. The immune network in pancreatic cancer development and progression. Oncogene 2013; 33: 2956-2967.
6. Arlt A, Schafer H, Kalthoff H. The 'N-factors' in pancreatic cancer: functional relevance of NF-kappaB, NFAT and Nrf2 in pancreatic cancer. Oncogenesis 2012; 1: e35.
7. Baumgart S, Ellenrieder V, Fernandez-Zapico ME. Oncogenic transcription factors: cornerstones of inflammation-linked pancreatic carcinogenesis. Gut 2013; 62: 310-316.
8. Arlt A, Gehrz A, Muerkoster S, Vorndamm J, Kruse ML, Folsch UR et al. Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene 2003; 22: 3243-3251.
9. 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.
10. Maier HJ, Wagner M, Schips TG, Salem HH, Baumann B, Wirth T. Requirement of NEMO/IKKgamma for effective expansion of KRAS-induced precancerous lesions in the pancreas. Oncogene 2012; 32: 2690-2695.
11. Perkins ND. The diverse and complex roles of NF-kappaB subunits in cancer. Nat Rev Cancer 2012; 12: 121-132.
12. Bang D, Wilson W, Ryan M, Yeh JJ, Baldwin AS. GSK-3alpha promotes oncogenic KRAS function in pancreatic cancer via TAK1-TAB stabilization and regulation of noncanonical NFkappaB. Cancer Discov 2013; 3: 690-703.
13. Sun SC. The noncanonical NF-kappaB pathway. Immunol Rev 2012; 246: 125-140.
14. Hamidi T, Algul H, Cano CE, Sandi MJ, Molejon MI, Riemann M et al. Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis. J Clin Invest 2012; 122: 2092-2103.
15. Wharry CE, Haines KM, Carroll RG, May MJ. Constitutive non-canonical NFkappaB signaling in pancreatic cancer cells. Cancer Biol Ther 2009; 8: 1567-1576.
16. Schneider G, Saur D, Siveke JT, Fritsch R, Greten FR, Schmid RM. IKKalpha controls p52/RelB at the skp2 gene promoter to regulate G1- to S-phase progression. EMBO J 2006; 25: 3801-3812.
17. Tchoghandjian A, Jennewein C, Eckhardt I, Rajalingam K, Fulda S. Identification of noncanonical NF-kappaB signaling as a critical mediator of Smac mimetic-stimulated migration and invasion of glioblastoma cells. Cell Death Dis 2013; 4: e564.
18. Egberts JH, Cloosters V, Noack A, Schniewind B, Thon L, Klose S et al. Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Res 2008; 68: 1443-1450.
19. Kurbitz C, Heise D, Redmer T, Goumas F, Arlt A, Lemke J et al. Epicatechin gallate and catechin gallate are superior to epigallocatechin gallate in growth suppression and anti-inflammatory activities in pancreatic tumor cells. Cancer Sci 2011; 102: 728-734.
20. Roder C, Trauzold A, Kalthoff H. Impact of death receptor signaling on the malignancy of pancreatic ductal adenocarcinoma. Eur J Cell Biol 2011; 90: 450-455.
21. Ling J, Kang Y, Zhao R, Xia Q, Lee DF, Chang Z et al. KrasG12D-induced IKK2/beta/NFkappaB activation by IL-1alpha and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma. Cancer Cell 2012; 21: 105-120.
22. Arlt A, Vorndamm J, Muerkoster S, Yu H, Schmidt WE, Folsch UR et al. Autocrine production of interleukin 1beta confers constitutive nuclear factor kappaB activity and chemoresistance in pancreatic carcinoma cell lines. Cancer Res 2002; 62: 910-916.
23. Muerkoster S, Wegehenkel K, Arlt A, Witt M, Sipos B, Kruse ML et al. Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin-1beta. Cancer Res 2004; 64: 1331-1337.
24. Kiefel H, Bondong S, Erbe-Hoffmann N, Hazin J, Riedle S, Wolf J et al. L1CAM-integrin interaction induces constitutive NF-kappaB activation in pancreatic adenocarcinoma cells by enhancing IL-1beta expression. Oncogene 2010; 29: 4766-4778.
25. Chen PH, Yang CR. Decoy receptor 3 expression in AsPC-1 human pancreatic adenocarcinoma cells via the phosphatidylinositol 3-kinase-, Akt-, and NF-kappa B-dependent pathway. J Immunol 2008; 181: 8441-8449.
26. Lemke J, Noack A, Adam D, Tchikov V, Bertsch U, Roder C et al. TRAIL signaling is mediated by DR4 in pancreatic tumor cells despite the expression of functional DR5. J Mol Med (Berl) 2010; 88: 729-740.
27. Trauzold A, Wermann H, Arlt A, Schutze S, Schafer H, Oestern S et al. CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells. Oncogene 2001; 20: 4258-4269.
28. Trauzold A, Roder C, Sipos B, Karsten K, Arlt A, Jiang P et al. CD95 and TRAF2 promote invasiveness of pancreatic cancer cells. FASEB J 2005; 19: 620-622.
29. Khanbolooki S, Nawrocki ST, Arumugam T, Andtbacka R, Pino MS, Kurzrock R et al. Nuclear factor-kappaB maintains TRAIL resistance in human pancreatic cancer cells. Molecular cancer therapeutics 2006; 5: 2251-2260.
30. Zhang JS, Herreros-Vilanueva M, Koenig A, Deng Z, de Narvajas AA, Gomez TS et al. Differential activity of GSK-3 isoforms regulates NF-kappaB and TRAIL- or TNFalpha induced apoptosis in pancreatic cancer cells. Cell Death Dis 2014; 5: e1142.
31. Braeuer SJ, Buneker C, Mohr A, Zwacka RM. Constitutively activated nuclear factor-kappaB, but not induced NF-kappaB, leads to TRAIL resistance by up-regulation of X-linked inhibitor of apoptosis protein in human cancer cells. Mol Cancer Res 2006; 4: 715-728.
32. Lu H, Yang X, Duggal P, Allen CT, Yan B, Cohen J et al. TNF-alpha promotes c-REL/DeltaNp63alpha interaction and TAp73 dissociation from key genes that mediate growth arrest and apoptosis in head and neck cancer. Cancer Res 2011; 71: 6867-6877.
33. King KE, Ponnamperuma RM, Allen C, Lu H, Duggal P, Chen Z et al. The p53 homologue DeltaNp63alpha interacts with the nuclear factor-kappaB pathway to modulate epithelial cell growth. Cancer Res 2008; 68: 5122-5131.
34. Belguise K, Sonenshein GE. PKCtheta promotes c-Rel-driven mammary tumorigenesis in mice and humans by repressing estrogen receptor alpha synthesis. J Clin Invest 2007; 117: 4009-4021.
35. Baumgart S, Glesel E, Singh G, Chen NM, Reutlinger K, Zhang J et al. Restricted heterochromatin formation links NFATc2 repressor activity with growth promotion in pancreatic cancer. Gastroenterology 2012; 142: 388-398 e381-387.
36. Koenig A, Linhart T, Schlengemann K, Reutlinger K, Wegele J, Adler G et al. NFAT-induced histone acetylation relay switch promotes c-Myc-dependent growth in pancreatic cancer cells. Gastroenterology 2010; 138: 1189-1199.
37. Singh SK, Baumgart S, Singh G, Konig AO, Reutlinger K, Hofbauer LC et al. Disruption of a nuclear NFATc2 protein stabilization loop confers breast and pancreatic cancer growth suppression by zoledronic acid. J Biol Chem 2011; 286: 28761-28771.
38. Konig A, Fernandez-Zapico ME, Ellenrieder V. Primers on molecular pathways - the NFAT transcription pathway in pancreatic cancer. Pancreatology 2010; 10: 416-422.
39. Wong D, Teixeira A, Oikonomopoulos S, Humburg P, Lone IN, Saliba D et al. Extensive characterization of NF-kappaB binding uncovers non-canonical motifs and advances the interpretation of genetic functional traits. Genome Biol 2011; 12: R70.
40. Cascinu S, Scartozzi M, Carbonari G, Pierantoni C, Verdecchia L, Mariani C et al. COX-2 and NF-KB overexpression is common in pancreatic cancer but does not predict for COX-2 inhibitors activity in combination with gemcitabine and oxaliplatin. Am J Clin Oncol 2007; 30: 526-530.
41. Shi S, Yao W, Xu J, Long J, Liu C, Yu X. Combinational therapy: new hope for pancreatic cancer?. Cancer Lett 2012; 317: 127-135.
42. Burkitt MD, Williams JM, Duckworth CA, O'Hara A, Hanedi A, Varro A et al. Signaling mediated by the NF-kappaB sub-units NF-kappaB1, NF-kappaB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice. Oncogene 2013; 32: 5563-5573.
43. Maity PC, Ray T, Das B, Sil AK. IKKbeta-I-kappaBvarepsilon-c-Rel/p50: a new axis of NF-kappaB activation in lung epithelial cells. Oncogenesis 2012; 1: e8.
44. Gilmore TDGerondakis S. The c-Rel transcription factor in development and disease. Genes Cancer 2011; 2: 695-711.
45. Ravi R, Bedi GC, Engstrom LW, Zeng Q, Mookerjee B, Gelinas C et al. Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB. Nat Cell Biol 2001; 3: 409-416.
46. Chen X, Kandasamy K, Srivastava RK. Differential roles of RelA (p65) and c-Rel subunits of nuclear factor kappa B in tumor necrosis factor-related apoptosis-inducing ligand signaling. Cancer Res 2003; 63: 1059-1066.
47. Morello S, Sorrentino R, Porta A, Forte G, Popolo A, Petrella A et al. Cl-IB-MECA enhances TRAIL-induced apoptosis via the modulation of NF-kappaB signalling pathway in thyroid cancer cells. J Cell Physiol 2009; 221: 378-386.
48. Griesmann H, Ripka S, Pralle M, Ellenrieder V, Baumgart S, Buchholz M et al. WNT5A-NFAT signaling mediates resistance to apoptosis in pancreatic cancer. Neoplasia (New York, NY 2013; 15: 11-22.
49. Robbs BK, Lucena PI, Viola JP. The transcription factor NFAT1 induces apoptosis through cooperation with Ras/Raf/MEK/ERK pathway and upregulation of TNF-alpha expression. Biochim Biophys Acta 2013; 1833: 2016-2028.
50. Duque J, Fresno M, Iniguez MA. Expression and function of the nuclear factor of activated T cells in colon carcinoma cells: involvement in the regulation of cyclooxygenase-2. J Biol Chem 2005; 280: 8686-8693.
51. Vazquez-Cedeira M, Lazo PA. Human VRK2 (vaccinia-related kinase 2) modulates tumor cell invasion by hyperactivation of NFAT1 and expression of cyclooxygenase-2. J Biol Chem 2012; 287: 42739-42750.
52. Iniguez MA, Martinez-Martinez S, Punzon C, Redondo JM, Fresno M. An essential role of the nuclear factor of activated T cells in the regulation of the expression of the cyclooxygenase-2 gene in human T lymphocytes. J Biol Chem 2000; 275: 23627-23635.
53. Cai T, Li X, Ding J, Luo W, Li JHuang C. A cross-talk between NFAT and NF-kappaB pathways is crucial for nickel-induced COX-2 expression in Beas-2B cells. Current Cancer Drug Targets 2011; 11: 548-559.
54. Hidalgo M. Pancreatic cancer. N Engl J Med 2010; 362: 1605-1617.
55. Rosevear HM, Lightfoot AJ, Griffith TS. Conatumumab, a fully human mAb against death receptor 5 for the treatment of cancer. Curr Opin Invest Drugs 2010; 11: 688-698.
56. Arlt A, Sebens S, Krebs S, Geismann C, Grossmann M, Kruse ML et al. Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity. Oncogene 2013; 32: 4825-4835.
57. Schuler S, Fritsche P, Diersch S, Arlt A, Schmid RM, Saur D et al. HDAC2 attenuates TRAIL-induced apoptosis of pancreatic cancer cells. Mol Cancer 2010; 9: 80.
58. Sahin IH, Hassan MM, Garrett CR. Impact of non-steroidal anti-inflammatory drugs on gastrointestinal cancers: current state-of-the science. Cancer Lett 2013; 345: 249-257.
59. Peulen O, Gonzalez A, Peixoto P, Turtoi A, Mottet D, Delvenne P et al. The anti-tumor effect of HDAC inhibition in a human pancreas cancer model is significantly improved by the simultaneous inhibition of cyclooxygenase 2. PLoS One 2013; 8: e75102.
60. Jendrossek V. Targeting apoptosis pathways by celecoxib in cancer. Cancer Lett 2013; 332: 313-324.
61. Wang W, Tam WF, Hughes CC, Rath S, Sen R. c-Rel is a target of pentoxifylline-mediated inhibition of T lymphocyte activation. Immunity 1997; 6: 165-174.
62. Jimenez JL, Punzon C, Navarro J, Munoz-Fernandez MA, Fresno M. Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappaB and nuclear factor of activated T cells activation. J Pharmacol Exp Therap 2001; 299: 753-759.
63. Yu R, Deedigan L, Albarenque SM, Mohr A, Zwacka RM. Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects. Cell Death Dis 2013; 4: e503.
64. Sebens Muerkoster S, Rausch AV, Isberner A, Minkenberg J, Blaszczuk E, Witt M et al. The apoptosis-inducing effect of gastrin on colorectal cancer cells relates to an increased IEX-1 expression mediating NF-kappa B inhibition. Oncogene 2008; 27: 1122-1134.
65. Stachel I, Geismann C, Aden K, Deisinger F, Rosenstiel P, Schreiber S et al. Modulation of nuclear factor E2-related factor-2 (Nrf2) activation by the stress response gene immediate early response-3 (IER3) in colonic epithelial cells: a novel mechanism of cellular adaption to inflammatory stress. J Biol Chem 2014; 289: 1917-1929.