Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression

BMC Cancer

Volumn 14, Issue 1, 2014, Pages

  Paschall, Amy V ^a   Zimmerman, Mary A ^a   Torres, Christina M ^a   Yang, Dafeng ^a   Chen, May R ^a   Li, Xia ^a   Bieberich, Erhard ^a   Bai, Aiping ^b   Bielawski, Jacek ^b   Bielawska, Alicja ^b   Liu, Kebin ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Apoptosis sensitization; Bcl xL; Ceramide; cIAP1; Fas; xIAP

Indexed keywords

ANTINEOPLASTIC AGENT; BV 6; C16 CERAMIDE; CERAMIDE DERIVATIVE; FAS ANTIGEN; LCL 85; PEPTIDES AND PROTEINS; PROTEASOME; PROTEIN BCL XL; PROTEIN CIAP1; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; X LINKED INHIBITOR OF APOPTOSIS;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL; CANCER RESISTANCE; CHEMOSENSITIVITY; COLON CANCER; CONTROLLED STUDY; DOSE RESPONSE; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG EXPOSURE; DRUG MECHANISM; DRUG MEGADOSE; DRUG POTENTIATION; DRUG TARGETING; GENE SILENCING; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LETHAL DOSE; LIVER TOXICITY; LOW DRUG DOSE; LUNG METASTASIS; METASTASIS INHIBITION; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; PRIMARY TUMOR; PROTEIN DEGRADATION; TOXICITY TESTING;

ANIMALS; ANTIGENS, CD95; ANTINEOPLASTIC AGENTS; APOPTOSIS; BREAST NEOPLASMS; CELL LINE, TUMOR; CERAMIDES; COLONIC NEOPLASMS; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; INHIBITOR OF APOPTOSIS PROTEINS; MICE; MICE, INBRED BALB C; MOLECULAR TARGETED THERAPY; PROPANOLAMINES; PYRIDINIUM COMPOUNDS; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TRANSFECTION; X-LINKED INHIBITOR OF APOPTOSIS PROTEIN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84892752237     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-14-24     Document Type: Article

References (50)

1. Caldwell SA, Ryan MH, McDuffie E, Abrams SI. The Fas/Fas ligand pathway is important for optimal tumor regression in a mouse model of CTL adoptive immunotherapy of experimental CMS4 lung metastases. J Immunol 2003, 171:2402-2412.
2. Strater J, Hinz U, Hasel C, Bhanot U, Mechtersheimer G, Lehnert T, Moller P. Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: clinical evidence for immunoselection and CD95L mediated control of minimal residual disease. Gut 2005, 54:661-665. 10.1136/gut.2004.052696, 1774512, 15831912.
3. Liu F, Bardhan K, Yang D, Thangaraju M, Ganapathy V, Waller JL, Liles GB, Lee JR, Liu K. NF-kappaB directly regulates fas transcription to modulate Fas-mediated apoptosis and tumor suppression. J Biol Chem 2012, 287:25530-25540. 10.1074/jbc.M112.356279, 3408167, 22669972.
4. Liu K. Role of apoptosis resistance in immune evasion and metastasis of colorectal cancer. World J Gastrointest Oncol 2010, 2:399-406. 10.4251/wjgo.v2.i11.399, 3000453, 21160903.
5. Villa-Morales M, Fernandez-Piqueras J. Targeting the Fas/FasL signaling pathway in cancer therapy. Expert Opin Ther Targets 2012, 16:85-101. 10.1517/14728222.2011.628937, 22239437.
6. Stewart TJ, Abrams SI. How tumours escape mass destruction. Oncogene 2008, 27:5894-5903. 10.1038/onc.2008.268, 18836470.
7. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000, 100:57-70. 10.1016/S0092-8674(00)81683-9, 10647931.
8. Moller P, Koretz K, Leithauser F, Bruderlein S, Henne C, Quentmeier A, Krammer PH. Expression of APO-1 (CD95), a member of the NGF/TNF receptor superfamily, in normal and neoplastic colon epithelium. Int J Cancer 1994, 57:371-377. 10.1002/ijc.2910570314, 8168998.
9. Keane MM, Ettenberg SA, Lowrey GA, Russell EK, Lipkowitz S. Fas expression and function in normal and malignant breast cell lines. Cancer Res 1996, 56:4791-4798.
10. Schillaci R, Salatino M, Cassataro J, Proietti CJ, Giambartolomei GH, Rivas MA, Carnevale RP, Charreau EH, Elizalde PV. Immunization with murine breast cancer cells treated with antisense oligodeoxynucleotides to type I insulin-like growth factor receptor induced an antitumoral effect mediated by a CD8+ response involving Fas/Fas ligand cytotoxic pathway. J Immunol 2006, 176:3426-3437.
11. Ponnusamy S, Meyers-Needham M, Senkal CE, Saddoughi SA, Sentelle D, Selvam SP, Salas A, Ogretmen B. Sphingolipids and cancer: ceramide and sphingosine-1-phosphate in the regulation of cell death and drug resistance. Future Oncol 2010, 6:1603-1624. 10.2217/fon.10.116, 3071292, 21062159.
12. Furuya H, Shimizu Y, Kawamori T. Sphingolipids in cancer. Cancer Metastasis Rev 2011, 30:567-576. 10.1007/s10555-011-9304-1, 22005951.
13. Camacho L, Meca-Cortes O, Abad JL, Garcia S, Rubio N, Diaz A, Celia-Terrassa T, Cingolani F, Bermudo R, Fernandez PL, Blanco J, Delgado A, Casas J, Fabrias G, Thomson TM. Acid ceramidase as a therapeutic target in metastatic prostate cancer. J Lipid Res 2013, 54:1207-1220. 10.1194/jlr.M032375, 23423838.
14. Alphonse G, Maalouf M, Battiston-Montagne P, Ardail D, Beuve M, Rousson R, Taucher-Scholz G, Fournier C, Rodriguez-Lafrasse C. p53-independent early and late apoptosis is mediated by ceramide after exposure of tumor cells to photon or carbon ion irradiation. BMC Cancer 2013, 13:151. 10.1186/1471-2407-13-151, 3621616, 23530619.
15. Salas A, Ponnusamy S, Senkal CE, Meyers-Needham M, Selvam SP, Saddoughi SA, Apohan E, Sentelle RD, Smith C, Gault CR, Obeid LM, El-Shewy HM, Oaks J, Santhanam R, Marcucci G, Baran Y, Mahajan S, Fernandes D, Stuart R, Perrotti D, Ogretmen B. Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A. Blood 2011, 117:5941-5952. 10.1182/blood-2010-08-300772, 3112039, 21527515.
16. Senkal CE, Ponnusamy S, Bielawski J, Hannun YA, Ogretmen B. Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways. Faseb J 2010, 24:296-308. 10.1096/fj.09-135087, 2797032, 19723703.
17. White-Gilbertson S, Mullen T, Senkal C, Lu P, Ogretmen B, Obeid L, Voelkel-Johnson C. Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells. Oncogene 2009, 28:1132-1141. 10.1038/onc.2008.468, 2648838, 19137010.
18. Krishnamurthy K, Wang G, Rokhfeld D, Bieberich E. Deoxycholate promotes survival of breast cancer cells by reducing the level of pro-apoptotic ceramide. Breast Cancer Res 2008, 10:R106. 10.1186/bcr2211, 2656903, 19087284.
19. Sauane M, Su ZZ, Dash R, Liu X, Norris JS, Sarkar D, Lee SG, Allegood JC, Dent P, Spiegel S, Fisher PB. Ceramide plays a prominent role in MDA-7/IL-24-induced cancer-specific apoptosis. J Cell Physiol 2010, 222:546-555.
20. Paris F, Grassme H, Cremesti A, Zager J, Fong Y, Haimovitz-Friedman A, Fuks Z, Gulbins E, Kolesnick R. Natural ceramide reverses Fas resistance of acid sphingomyelinase(-/-) hepatocytes. J Biol Chem 2001, 276:8297-8305. 10.1074/jbc.M008732200, 11096096.
21. Cremesti A, Paris F, Grassme H, Holler N, Tschopp J, Fuks Z, Gulbins E, Kolesnick R. Ceramide enables fas to cap and kill. J Biol Chem 2001, 276:23954-23961. 10.1074/jbc.M101866200, 11287428.
22. Park MA, Zhang G, Martin AP, Hamed H, Mitchell C, Hylemon PB, Graf M, Rahmani M, Ryan K, Liu X, Spiegel S, Norris J, Fisher PB, Grant S, Dent P. Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation. Cancer Biol Ther 2008, 7:1648-1662. 10.4161/cbt.7.10.6623, 2674577, 18787411.
23. Grassme H, Cremesti A, Kolesnick R, Gulbins E. Ceramide-mediated clustering is required for CD95-DISC formation. Oncogene 2003, 22:5457-5470. 10.1038/sj.onc.1206540, 12934106.
24. Yoon G, Kim KO, Lee J, Kwon D, Shin JS, Kim SJ, Choi IH. Ceramide increases Fas-mediated apoptosis in glioblastoma cells through FLIP down-regulation. J Neurooncol 2002, 60:135-141. 10.1023/A:1020604705831, 12635660.
25. Caricchio R, D'Adamio L, Cohen PL. Fas, ceramide and serum withdrawal induce apoptosis via a common pathway in a type II Jurkat cell line. Cell Death Differ 2002, 9:574-580. 10.1038/sj.cdd.4400996, 11973615.
26. Yacoub A, Hamed HA, Allegood J, Mitchell C, Spiegel S, Lesniak MS, Ogretmen B, Dash R, Sarkar D, Broaddus WC, Grant S, Curiel DT, Fisher PB, Dent P. PERK-dependent regulation of ceramide synthase 6 and thioredoxin play a key role in mda-7/IL-24-induced killing of primary human glioblastoma multiforme cells. Cancer Res 2010, 70:1120-1129. 10.1158/0008-5472.CAN-09-4043, 2890071, 20103619.
27. Morales A, Paris R, Villanueva A, Llacuna L, Garcia-Ruiz C, Fernandez-Checa JC. Pharmacological inhibition or small interfering RNA targeting acid ceramidase sensitizes hepatoma cells to chemotherapy and reduces tumor growth in vivo. Oncogene 2007, 26:905-916. 10.1038/sj.onc.1209834, 16862171.
28. Park MA, Mitchell C, Zhang G, Yacoub A, Allegood J, Haussinger D, Reinehr R, Larner A, Spiegel S, Fisher PB, Voelkel-Johnson C, Ogretmen B, Grant S, Dent P. Vorinostat and sorafenib increase CD95 activation in gastrointestinal tumor cells through a Ca(2+)-de novo ceramide-PP2A-reactive oxygen species-dependent signaling pathway. Cancer Res 2010, 70:6313-6324. 10.1158/0008-5472.CAN-10-0999, 2918282, 20631069.
29. Bielawska A, Bielawski J, Szulc ZM, Mayroo N, Liu X, Bai A, Elojeimy S, Rembiesa B, Pierce J, Norris JS, Hannun YA. Novel analogs of D-e-MAPP and B13. Part 2: signature effects on bioactive sphingolipids. Bioorg Med Chem 2008, 16:1032-1045. 10.1016/j.bmc.2007.08.032, 2268750, 17881234.
30. Liu F, Hu X, Zimmerman M, Waller J, Wu P, Hayes-Jordan A, Lev D, Liu K. TNFα Cooperates with IFN-γ to Repress Bcl-xL Expression to Sensitize Metastatic Colon Carcinoma Cells to TRAIL-mediated Apoptosis. PLoS ONE 2011, 6:e16241. 10.1371/journal.pone.0016241, 3022032, 21264227.
31. Hu X, Zimmerman MA, Bardhan K, Yang D, Waller JL, Liles GB, Lee JR, Pollock R, Lev D, Ware CF, Garber E, Bailly V, Browning JL, Liu K. Lymphotoxin beta receptor mediates caspase-dependent tumor cell apoptosis in vitro and tumor suppression in vivo despite induction of NF-kappaB activation. Carcinogenesis 2013, 34:1105-1114. 10.1093/carcin/bgt014, 23349015.
32. Hu X, Bardhan K, Paschall AV, Yang D, Waller JL, Park MA, Nayak-Kapoor A, Samuel TA, Abrams SI, Liu K. Deregulation of apoptotic factors bcl-xl and bax confers apoptotic resistance to Myeloid-derived suppressor cells and contributes to their persistence in cancer. J Biol Chem 2013, 288:19103-19115. 10.1074/jbc.M112.434530, 23677993.
33. Zimmerman MA, Rahman NT, Yang D, Lahat G, Lazar AJ, Pollock R, Lev D, Liu K. Unphosphorylated STAT1 promotes sarcoma development by repressing expression of Fas and Bad and conferring apoptotic resistance. Cancer Res 2012, 72:4724-4732. 10.1158/0008-5472.CAN-12-1347, 3564959, 22805310.
34. Yang D, Torres CM, Bardhan K, Zimmerman M, McGaha TL, Liu K. Decitabine and vorinostat cooperate to sensitize colon carcinoma cells to fas ligand-induced apoptosis in vitro and tumor suppression in vivo. J Immunol 2012, 188:4441-4449. 10.4049/jimmunol.1103035, 3398838, 22461695.
35. Dueber EC, Schoeffler AJ, Lingel A, Elliott JM, Fedorova AV, Giannetti AM, Zobel K, Maurer B, Varfolomeev E, Wu P, Wallweber HJ, Hymowitz SG, Deshayes K, Vucic D, Fairbrother WJ. Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination. Science 2011, 334:376-380. 10.1126/science.1207862, 22021857.
36. Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, Zobel K, Dynek JN, Elliott LO, Wallweber HJ, Flygare JA, Fairbrother WJ, Deshayes K, Dixit VM, Vucic D. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 2007, 131:669-681. 10.1016/j.cell.2007.10.030, 18022362.
37. Varfolomeev E, Goncharov T, Maecker H, Zobel K, Komuves LG, Deshayes K, Vucic D. Cellular Inhibitors of Apoptosis Are Global Regulators of NF-kappaB and MAPK Activation by Members of the TNF Family of Receptors. Sci Signal 2012, 5:ra22.
38. Chalfant CE, Rathman K, Pinkerman RL, Wood RE, Obeid LM, Ogretmen B, Hannun YA. De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. J Biol Chem 2002, 277:12587-12595. 10.1074/jbc.M112010200, 11801602.
39. Siskind LJ, Mullen TD, Romero Rosales K, Clarke CJ, Hernandez-Corbacho MJ, Edinger AL, Obeid LM. The BCL-2 protein BAK is required for long-chain ceramide generation during apoptosis. J Biol Chem 2010, 285:11818-11826. 10.1074/jbc.M109.078121, 2852918, 20172858.
40. Lee H, Rotolo JA, Mesicek J, Penate-Medina T, Rimner A, Liao WC, Yin X, Ragupathi G, Ehleiter D, Gulbins E, Zhai D, Reed JC, Haimovitz-Friedman A, Fuks Z, Kolesnick R. Mitochondrial ceramide-rich macrodomains functionalize Bax upon irradiation. PLoS One 2011, 6:e19783. 10.1371/journal.pone.0019783, 3113798, 21695182.
41. Chipuk JE, McStay GP, Bharti A, Kuwana T, Clarke CJ, Siskind LJ, Obeid LM, Green DR. Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis. Cell 2012, 148:988-1000. 10.1016/j.cell.2012.01.038, 3506012, 22385963.
42. Beverly LJ, Howell LA, Hernandez-Corbacho M, Casson L, Chipuk JE, Siskind LJ. BAK activation is necessary and sufficient to drive ceramide synthase-dependent ceramide accumulation following inhibition of BCL2-like proteins. Biochem J 2013, 452:111-119. 3642864, 23480852.
43. Casson L, Howell L, Mathews LA, Ferrer M, Southall N, Guha R, Keller JM, Thomas C, Siskind LJ, Beverly LJ. Inhibition of ceramide metabolism sensitizes human leukemia cells to inhibition of BCL2-like proteins. PLoS One 2013, 8:e54525. 10.1371/journal.pone.0054525, 3546986, 23342165.
44. Jost PJ, Grabow S, Gray D, McKenzie MD, Nachbur U, Huang DC, Bouillet P, Thomas HE, Borner C, Silke J, Strasser A, Kaufmann T. XIAP discriminates between type I and type II FAS-induced apoptosis. Nature 2009, 460:1035-1039. 10.1038/nature08229, 2956120, 19626005.
45. Vince JE, Wong WW, Khan N, Feltham R, Chau D, Ahmed AU, Benetatos CA, Chunduru SK, Condon SM, McKinlay M, Brink R, Leverkus M, Tergaonkar V, Schneider P, Callus BA, Koentgen F, Vaux DL, Silke J. IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis. Cell 2007, 131:682-693. 10.1016/j.cell.2007.10.037, 18022363.
46. Varfolomeev E, Alicke B, Elliott JM, Zobel K, West K, Wong H, Scheer JM, Ashkenazi A, Gould SE, Fairbrother WJ, Vucic D. X chromosome-linked inhibitor of apoptosis regulates cell death induction by proapoptotic receptor agonists. J Biol Chem 2009, 284:34553-34560. 10.1074/jbc.M109.040139, 2787317, 19854829.
47. Separovic D, Joseph N, Breen P, Bielawski J, Pierce JS, Buren EV, Bhatti G, Saad ZH, Bai A, Bielawska A. Combining anticancer agents photodynamic therapy and LCL85 leads to distinct changes in the sphingolipid profile, autophagy, caspase-3 activation in the absence of cell death, and long-term sensitization. Biochem Biophys Res Commun 2011, 409:372-377. 10.1016/j.bbrc.2011.04.091, 3123537, 21545791.
48. Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R, von Boehmer H, von Andrian UH. Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 2006, 25:129-141. 10.1016/j.immuni.2006.04.015, 16860762.
49. Chen ML, Pittet MJ, Gorelik L, Flavell RA, Weissleder R, von Boehmer H, Khazaie K. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc Natl Acad Sci USA 2005, 102:419-424. 10.1073/pnas.0408197102, 544311, 15623559.
50. Rotolo JA, Stancevic B, Lu SX, Zhang J, Suh D, King CG, Kappel LW, Murphy GF, Liu C, Fuks Z, van den Brink MR, Kolesnick R. Cytolytic T cells induce ceramide-rich platforms in target cell membranes to initiate graft-versus-host disease. Blood 2009, 114:3693-3706. 10.1182/blood-2008-11-191148, 2766684, 19666872.