Skip to main content
SpringerLink
Log in

Role of Sphingolipids in Death Receptor Signalling

  • Chapter
  • First Online:
Book cover TRAIL, Fas Ligand, TNF and TLR3 in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 12))

  • 640 Accesses

Abstract

Sphingolipids (SLs) are sphingoid base-containing lipids, which are enriched in plasma membrane microdomains. Some SLs behave as bioactive molecules, modulating cell signalling in various pathophysiological contexts. Whereas ceramide triggers apoptosis and impairs cell migration, sphingosine-1-phosphate (S1P) induces the opposite effects. CD95/Fas, TRAIL-R1 (DR4), and TRAIL-R2 (DR5) are death receptors (DRs) and members of the TNF-R1 superfamily. DRs trigger apoptosis of various cell types, including cancer cells. Over the last two decades, a growing body of evidence indicates that SLs modulate DR signalling. DR stimulation triggers the generation of SLs, including ceramide, sphingosine, and gangliosides. Ceramide has been reported to facilitate DR clustering into lipid rafts upon pro-apoptotic DR agonists. Moreover, ceramide and its metabolites likely contribute to the mitochondrial route of apoptosis. More recently, SLs have been shown to modulate CD95-mediated cell migration of triple negative breast cancer cell lines and Th17 lymphoid cells in response to a nonapoptotic form of CD95L. Herein, we review the role of SLs in DR signalling, including apoptotic and migration pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hanada K (2003) Serine palmitoyltransferase, a key enzyme of sphingolipid metabolism. Biochim Biophys Acta 1632:16–30

    Article  CAS  PubMed  Google Scholar 

  2. Levy M, Futerman AH (2010) Mammalian ceramide synthases. IUBMB Life 62:347–356. doi:10.1002/iub.319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tafesse FG, Ternes P, Holthuis JCM (2006) The multigenic sphingomyelin synthase family. J Biol Chem 281:29421–29425. doi:10.1074/jbc.R600021200

    Article  CAS  PubMed  Google Scholar 

  4. Lahiri S, Futerman AH (2007) The metabolism and function of sphingolipids and glycosphingolipids. Cell Mol Life Sci CMLS 64:2270–2284. doi:10.1007/s00018-007-7076-0

    Article  CAS  PubMed  Google Scholar 

  5. Van Overloop H, Gijsbers S, Van Veldhoven PP (2006) Further characterization of mammalian ceramide kinase: substrate delivery and (stereo)specificity, tissue distribution, and subcellular localization studies. J Lipid Res 47:268–283. doi:10.1194/JLR.M500321-JLR200

    Article  PubMed  Google Scholar 

  6. Hait NC, Oskeritzian CA, Paugh SW et al (2006) Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta 1758:2016–2026. doi:10.1016/j.Bbamem.2006.08.007

    Article  CAS  PubMed  Google Scholar 

  7. Mao C, Obeid LM (2008) Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate. Biochim Biophys Acta 1781:424–434. doi:10.1016/j.Bbalip.2008.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sabourdy F, Kedjouar B, Sorli SC et al (2008) Functions of sphingolipid metabolism in mammals—lessons from genetic defects. Biochim Biophys Acta 1781:145–183. doi:10.1016/j.Bbalip.2008.01.004

    Article  CAS  PubMed  Google Scholar 

  9. Astudillo L, Sabourdy F, Therville N et al (2015) Human genetic disorders of sphingolipid biosynthesis. J Inherit Metab Dis 38:65–76. doi:10.1007/s10545-014-9736-1

    Article  CAS  PubMed  Google Scholar 

  10. Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572. doi:10.1038/42408

    Article  CAS  PubMed  Google Scholar 

  11. Simons K, Ehehalt R (2002) Cholesterol, lipid rafts, and disease. J Clin Invest 110:597–603. doi:10.1172/JCI16390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Grassme H, Jekle A, Riehle A et al (2001) CD95 signaling via ceramide-rich membrane rafts. J Biol Chem 276:20589–20596. doi:10.1074/jbc.M101207200

    Article  CAS  PubMed  Google Scholar 

  13. Muppidi JR, Siegel RM (2004) Ligand-independent redistribution of Fas (CD95) into lipid rafts mediates clonotypic T cell death. Nat Immunol 5:182–189. doi:10.1038/ni1024

    Article  CAS  PubMed  Google Scholar 

  14. Legembre P, Daburon S, Moreau P et al (2005) Amplification of Fas-mediated apoptosis in type II cells via microdomain recruitment. Mol Cell Biol 25:6811–6820. doi:10.1128/MCB.25.15.6811-6820.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gault CR, Obeid LM, Hannun YA (2010) An overview of sphingolipid metabolism: from synthesis to breakdown. Adv Exp Med Biol 688:1–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nurminen TA, Holopainen JM, Zhao H, Kinnunen PKJ (2002) Observation of topical catalysis by sphingomyelinase coupled to microspheres. J Am Chem Soc 124:12129–12134

    Article  CAS  PubMed  Google Scholar 

  17. Grassmé H, Schwarz H, Gulbins E (2001) Molecular mechanisms of ceramide-mediated CD95 clustering. Biochem Biophys Res Commun 284:1016–1030. doi:10.1006/bbrc.2001.5045

    Article  PubMed  Google Scholar 

  18. Miyaji M, Jin Z-X, Yamaoka S et al (2005) Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis. J Exp Med 202:249–259. doi:10.1084/jem.20041685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Brenner B, Ferlinz K, Grassmé H et al (1998) Fas/CD95/Apo-I activates the acidic sphingomyelinase via caspases. Cell Death Differ 5:29–37. doi:10.1038/sj.Cdd.4400307

    Article  CAS  PubMed  Google Scholar 

  20. Grullich C, Sullards MC, Fuks Z et al (2000) CD95(Fas/APO-1) signals ceramide generation independent of the effector stage of apoptosis. J Biol Chem 275:8650–8656

    Article  CAS  PubMed  Google Scholar 

  21. Grassmé H, Cremesti A, Kolesnick R, Gulbins E (2003) Ceramide-mediated clustering is required for CD95-DISC formation. Oncogene 22:5457–5470. doi:10.1038/sj.Onc.1206540

    Article  PubMed  Google Scholar 

  22. Gulbins E, Kolesnick R (2000) Measurement of sphingomyelinase activity. Methods Enzymol 322:382–388

    Article  CAS  PubMed  Google Scholar 

  23. Perrotta C, Bizzozero L, Cazzato D et al (2010) Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function. J Biol Chem 285:40240–40251. doi:10.1074/jbc.M110.139287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Grassmé H, Bock J, Kun J, Gulbins E (2002) Clustering of CD40 ligand is required to form a functional contact with CD40. J Biol Chem 277:30289–30299. doi:10.1074/jbc.M200494200

    Article  PubMed  Google Scholar 

  25. Grassmé H, Riethmüller J, Gulbins E (2007) Biological aspects of ceramide-enriched membrane domains. Prog Lipid Res 46:161–170. doi:10.1016/j.Plipres.2007.03.002

    Article  PubMed  Google Scholar 

  26. Lin T, Genestier L, Pinkoski MJ et al (2000) Role of acidic sphingomyelinase in Fas/CD95-mediated cell death. J Biol Chem 275:8657–8663

    Article  CAS  PubMed  Google Scholar 

  27. Paris F, Grassmé H, Cremesti A et al (2001) Natural ceramide reverses Fas resistance of acid sphingomyelinase(−/−) hepatocytes. J Biol Chem 276:8297–8305. doi:10.1074/jbc.M008732200

    Article  CAS  PubMed  Google Scholar 

  28. De Maria R, Rippo MR, Schuchman EH, Testi R (1998) Acidic sphingomyelinase (ASM) is necessary for fas-induced GD3 ganglioside accumulation and efficient apoptosis of lymphoid cells. J Exp Med 187:897–902

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cock JG, Tepper AD, de Vries E et al (1998) CD95 (Fas/APO-1) induces ceramide formation and apoptosis in the absence of a functional acid sphingomyelinase. J Biol Chem 273:7560–7565

    Article  CAS  PubMed  Google Scholar 

  30. Bezombes C, Ségui B, Cuvillier O et al (2001) Lysosomal sphingomyelinase is not solicited for apoptosis signaling. FASEB J 15:297–299. doi:10.1096/fj.00-0466fje

    CAS  PubMed  Google Scholar 

  31. Chalfant CE, Ogretmen B, Galadari S et al (2001) FAS activation induces dephosphorylation of SR proteins; dependence on the de novo generation of ceramide and activation of protein phosphatase 1. J Biol Chem 276:44848–44855. doi:10.1074/jbc.M106291200

    Article  CAS  PubMed  Google Scholar 

  32. Watanabe M, Kitano T, Kondo T et al (2004) Increase of nuclear ceramide through caspase-3-dependent regulation of the “sphingomyelin cycle” in Fas-induced apoptosis. Cancer Res 64:1000–1007

    Article  CAS  PubMed  Google Scholar 

  33. Lafont E, Milhas D, Carpentier S et al (2010) Caspase-mediated inhibition of sphingomyelin synthesis is involved in FasL-triggered cell death. Cell Death Differ 17:642–654. doi:10.1038/cdd.2009.130

    Article  CAS  PubMed  Google Scholar 

  34. Tepper AD, de Vries E, van Blitterswijk WJ, Borst J (1999) Ordering of ceramide formation, caspase activation, and mitochondrial changes during CD95- and DNA damage-induced apoptosis. J Clin Invest 103:971–978. doi:10.1172/JCI5457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Juo P, Woo MS, Kuo CJ et al (1999) FADD is required for multiple signaling events downstream of the receptor Fas. Cell Growth Differ 10:797–804

    CAS  PubMed  Google Scholar 

  36. Cuvillier O, Edsall L, Spiegel S (2000) Involvement of sphingosine in mitochondria-dependent Fas-induced apoptosis of type II Jurkat T cells. J Biol Chem 275:15691–15700. doi:10.1074/jbc.M000280200

    Article  CAS  PubMed  Google Scholar 

  37. Tepper AD, Cock JG, de Vries E et al (1997) CD95/Fas-induced ceramide formation proceeds with slow kinetics and is not blocked by caspase-3/CPP32 inhibition. J Biol Chem 272:24308–24312

    Article  CAS  PubMed  Google Scholar 

  38. Lafont E, Dupont R, Andrieu-Abadie N et al (2012) Ordering of ceramide formation and caspase-9 activation in CD95L-induced Jurkat leukemia T cell apoptosis. Biochim Biophys Acta 1821:684–693. doi:10.1016/j.Bbalip.2012.01.012

    Article  CAS  PubMed  Google Scholar 

  39. Samraj AK, Keil E, Ueffing N et al (2006) Loss of caspase-9 provides genetic evidence for the type I/II concept of CD95-mediated apoptosis. J Biol Chem 281:29652–29659. doi:10.1074/jbc.M603487200

    Article  CAS  PubMed  Google Scholar 

  40. Movsesyan VA, Yakovlev AG, Dabaghyan EA et al (2002) Ceramide induces neuronal apoptosis through the caspase-9/caspase-3 pathway. Biochem Biophys Res Commun 299:201–207

    Article  CAS  PubMed  Google Scholar 

  41. Nica AF, Tsao CC, Watt JC et al (2008) Ceramide promotes apoptosis in chronic myelogenous leukemia-derived K562 cells by a mechanism involving caspase-8 and JNK. Cell Cycle 7:3362–3370. doi:10.4161/cc.7.21.6894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Milhas D, Andrieu-Abadie N, Levade T et al (2012) The tricyclodecan-9-yl-xanthogenate D609 triggers ceramide increase and enhances FasL-induced caspase-dependent and -independent cell death in T lymphocytes. Int J Mol Sci 13:8834–8852. doi:10.3390/ijms13078834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Milhas D, Cuvillier O, Therville N et al (2005) Caspase-10 triggers Bid cleavage and caspase cascade activation in FasL-induced apoptosis. J Biol Chem 280:19836–19842. doi:10.1074/jbc.M414358200

    Article  CAS  PubMed  Google Scholar 

  44. Ganesan V, Perera MN, Colombini D et al (2010) Ceramide and activated Bax act synergistically to permeabilize the mitochondrial outer membrane. Apoptosis 15:553–562. doi:10.1007/s10495-009-0449-0

    Article  CAS  PubMed  Google Scholar 

  45. Chipuk JE, McStay GP, Bharti A et al (2012) Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis. Cell 148:988–1000. doi:10.1016/j.Cell.2012.01.038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zundel W, Giaccia A (1998) Inhibition of the anti-apoptotic PI(3)K/Akt/Bad pathway by stress. Genes Dev 12:1941–1946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Chalfant CE, Rathman K, Pinkerman RL et al (2002) 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 277:12587–12595. doi:10.1074/jbc.M112010200

    Article  CAS  PubMed  Google Scholar 

  48. De Maria R, Lenti L, Malisan F et al (1997) Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis. Science 277:1652–1655

    Article  PubMed  Google Scholar 

  49. Popa I, Therville N, Carpentier S et al (2011) Production of multiple brain-like ganglioside species is dispensable for fas-induced apoptosis of lymphoid cells. PLoS One 6:e19974. doi:10.1371/journal.Pone.0019974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kang N-Y, Kang Y, Kang S-K et al (2006) Transcriptional regulation of the human GD3 synthase gene expression in Fas-induced Jurkat T cells: a critical role of transcription factor NF-kappaB in regulated expression. Glycobiology 16:375–389. doi:10.1093/glycob/cwj087

    Article  CAS  PubMed  Google Scholar 

  51. Sorice M, Matarrese P, Tinari A et al (2009) Raft component GD3 associates with tubulin following CD95/Fas ligation. FASEB J 23:3298–3308. doi:10.1096/fj.08-128140

    Article  CAS  PubMed  Google Scholar 

  52. Sorice M, Matarrese P, Manganelli V et al (2010) Role of GD3-CLIPR-59 association in lymphoblastoid T cell apoptosis triggered by CD95/Fas. PLoS One 5:e8567. doi:10.1371/journal.Pone.0008567

    Article  PubMed  PubMed Central  Google Scholar 

  53. Peter ME, Hadji A, Murmann AE et al (2015) The role of CD95 and CD95 ligand in cancer. Cell Death Differ 22:549–559. doi:10.1038/cdd.2015.3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Malleter M, Tauzin S, Bessede A et al (2013) CD95L cell surface cleavage triggers a prometastatic signaling pathway in triple-negative breast cancer. Cancer Res 73:6711–6721. doi:10.1158/0008-5472.CAN-13-1794

    Article  CAS  PubMed  Google Scholar 

  55. Fouqué A, Debure L, Legembre P (2014) The CD95/CD95L signaling pathway: a role in carcinogenesis. Biochim Biophys Acta 1846:130–141. doi:10.1016/j.Bbcan.2014.04.007

    PubMed  Google Scholar 

  56. Suda T, Hashimoto H, Tanaka M et al (1997) Membrane Fas ligand kills human peripheral blood T lymphocytes, and soluble Fas ligand blocks the killing. J Exp Med 186:2045–2050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Schneider P, Holler N, Bodmer JL et al (1998) Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity. J Exp Med 187:1205–1213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. O’Reilly LA, Tai L, Lee L et al (2009) Membrane-bound Fas ligand only is essential for Fas-induced apoptosis. Nature 461:659–663. doi:10.1038/nature08402

    Article  Google Scholar 

  59. Kischkel FC, Hellbardt S, Behrmann I et al (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J 14:5579–5588

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Tauzin S, Chaigne-Delalande B, Selva E et al (2011) The naturally processed CD95L elicits a c-yes/calcium/PI3K-driven cell migration pathway. PLoS Biol 9:e1001090. doi:10.1371/journal.Pbio.1001090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Khadra N, Bresson-Bepoldin L, Penna A et al (2011) CD95 triggers Orai1-mediated localized Ca2+ entry, regulates recruitment of protein kinase C (PKC) β2, and prevents death-inducing signaling complex formation. Proc Natl Acad Sci U S A 108:19072–19077. doi:10.1073/pnas.1116946108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Monet M, Poët M, Tauzin S et al (2016) The cleaved FAS ligand activates the Na(+)/H(+) exchanger NHE1 through Akt/ROCK1 to stimulate cell motility. Sci Rep 6:28008. doi:10.1038/srep28008

    Article  PubMed  PubMed Central  Google Scholar 

  63. Edmond V, Dufour F, Poiroux G et al (2015) Downregulation of ceramide synthase-6 during epithelial-to-mesenchymal transition reduces plasma membrane fluidity and cancer cell motility. Oncogene 34:996–1005. doi:10.1038/onc.2014.55

    Article  CAS  PubMed  Google Scholar 

  64. Hannun YA, Obeid LM (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9:139–150. doi:10.1038/nrm2329

    Article  CAS  PubMed  Google Scholar 

  65. Mullen TD, Hannun YA, Obeid LM (2012) Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J 441:789–802. doi:10.1042/BJ20111626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Goñi FM, Alonso A (2009) Effects of ceramide and other simple sphingolipids on membrane lateral structure. Biochim Biophys Acta 1788:169–177. doi:10.1016/j.Bbamem.2008.09.002

    Article  PubMed  Google Scholar 

  67. Pewzner-Jung Y, Park H, Laviad EL et al (2010) A critical role for ceramide synthase 2 in liver homeostasis: I. Alterations in lipid metabolic pathways. J Biol Chem 285:10902–10910. doi:10.1074/jbc.M109.077594

  68. Levade T, Andrieu-Abadie N, Micheau O et al (2015) Sphingolipids modulate the epithelial–mesenchymal transition in cancer. Cell Death Discov 1:15001. doi:10.1038/cddiscovery.2015.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Poissonnier A, Sanséau D, Le Gallo M et al (2016) CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice. Immunity 45:209–223. doi:10.1016/j.Immuni.2016.06.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hait NC, Sarkar S, Le Stunff H et al (2005) Role of sphingosine kinase 2 in cell migration toward epidermal growth factor. J Biol Chem 280:29462–29469. doi:10.1074/jbc.M502922200

  71. Sarkar S, Maceyka M, Hait NC et al (2005) Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells. FEBS Lett 579:5313–5317. doi:10.1016/j.Febslet.2005.08.055

    Article  CAS  PubMed  Google Scholar 

  72. Ashkenazi A, Holland P, Eckhardt SG (2008) Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL). J Clin Oncol 26:3621–3630. doi:10.1200/JCO.2007.15.7198

    Article  CAS  PubMed  Google Scholar 

  73. LeBlanc H, Lawrence D, Varfolomeev E et al (2002) Tumor-cell resistance to death receptor—induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med 8:274–281. doi:10.1038/nm0302-274

    Article  CAS  PubMed  Google Scholar 

  74. Ndozangue-Touriguine O, Sebbagh M, Mérino D et al (2008) A mitochondrial block and expression of XIAP lead to resistance to TRAIL-induced apoptosis during progression to metastasis of a colon carcinoma. Oncogene 27:6012–6022. doi:10.1038/onc.2008.197

    Article  CAS  PubMed  Google Scholar 

  75. Micheau O, Shirley S, Dufour F (2013) Death receptors as targets in cancer. Br J Pharmacol 169:1723–1744. doi:10.1111/bph.12238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Wiley SR, Schooley K, Smolak PJ et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682

    Article  CAS  PubMed  Google Scholar 

  77. Almasan A, Ashkenazi A (2003) Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy. Cytokine Growth Factor Rev 14:337–348

    Article  CAS  PubMed  Google Scholar 

  78. Mérino D, Lalaoui N, Morizot A et al (2007) TRAIL in cancer therapy: present and future challenges. Expert Opin Ther Targets 11:1299–1314. doi:10.1517/14728222.11.10.1299

    Article  PubMed  PubMed Central  Google Scholar 

  79. Dumitru CA, Gulbins E (2006) TRAIL activates acid sphingomyelinase via a redox mechanism and releases ceramide to trigger apoptosis. Oncogene 25:5612–5625. doi:10.1038/sj.Onc.1209568

    Article  CAS  PubMed  Google Scholar 

  80. Xiang H, Reyes AE, Eppler S et al (2013) Death receptor 5 agonistic antibody PRO95780: preclinical pharmacokinetics and concentration-effect relationship support clinical dose and regimen selection. Cancer Chemother Pharmacol 72:405–415. doi:10.1007/s00280-013-2200-3

    Article  CAS  PubMed  Google Scholar 

  81. Walczak H, Krammer PH (2000) The CD95 (APO-1/Fas) and the TRAIL (APO-2L) apoptosis systems. Exp Cell Res 256:58–66. doi:10.1006/excr.2000.4840

    Article  CAS  PubMed  Google Scholar 

  82. Pettus BJ, Chalfant CE, Hannun YA (2002) Ceramide in apoptosis: an overview and current perspectives. Biochim Biophys Acta 1585:114–125

    Article  CAS  PubMed  Google Scholar 

  83. Ségui B, Andrieu-Abadie N, Jaffrézou J-P et al (2006) Sphingolipids as modulators of cancer cell death: potential therapeutic targets. Biochim Biophys Acta 1758:2104–2120. doi:10.1016/j.Bbamem.2006.05.024

    Article  PubMed  Google Scholar 

  84. Truman J-P, García-Barros M, Obeid LM, Hannun YA (2014) Evolving concepts in cancer therapy through targeting sphingolipid metabolism. Biochim Biophys Acta 1841:1174–1188. doi:10.1016/j.Bbalip.2013.12.013

    Article  CAS  PubMed  Google Scholar 

  85. Thon L, Mathieu S, Kabelitz D, Adam D (2006) The murine TRAIL receptor signals caspase-independent cell death through ceramide. Exp Cell Res 312:3808–3821. doi:10.1016/j.Yexcr.2006.08.017

    Article  CAS  PubMed  Google Scholar 

  86. White-Gilbertson S, Mullen T, Senkal C et al (2009) Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells. Oncogene 28:1132–1141. doi:10.1038/onc.2008.468

  87. Skender B, Hofmanová J, Slavík J et al (2014) DHA-mediated enhancement of TRAIL-induced apoptosis in colon cancer cells is associated with engagement of mitochondria and specific alterations in sphingolipid metabolism. Biochim Biophys Acta 1841:1308–1317. doi:10.1016/j.Bbalip.2014.06.005

    Article  CAS  PubMed  Google Scholar 

  88. Voelkel-Johnson C, Hannun YA, El-Zawahry A (2005) Resistance to TRAIL is associated with defects in ceramide signaling that can be overcome by exogenous C6-ceramide without requiring down-regulation of cellular FLICE inhibitory protein. Mol Cancer Ther 4:1320–1327. doi:10.1158/1535-7163.MCT-05-0086

    Article  CAS  PubMed  Google Scholar 

  89. Yang J, Yang C, Zhang S et al (2015) ABC294640, a sphingosine kinase 2 inhibitor, enhances the antitumor effects of TRAIL in non-small cell lung cancer. Cancer Biol Ther 16:1194–1204. doi:10.1080/15384047.2015.1056944

    Article  PubMed  PubMed Central  Google Scholar 

  90. Woo SM, Seo BR, Min K, Kwon TK (2015) FTY720 enhances TRAIL-mediated apoptosis by up-regulating DR5 and down-regulating Mcl-1 in cancer cells. Oncotarget 6:11614–11626. doi:10.18632/oncotarget.3426

Download references

Acknowledgements

This work was supported by Ligue nationale contre le cancer, Institut National du Cancer (INCa), INSERM and Paul Sabatier University (Toulouse III). FB is a recipient of a grant from Association de Spécialisation et d’Orientation Scientifique.

Author information

Authors and Affiliations

  1. INSERM UMR 1037, CRCT, 31037, Toulouse, France

    Fatima Bilal, Michaël Pérès, Nathalie Andrieu-Abadie, Thierry Levade & Bruno Ségui

  2. Equipe Labellisée Ligue Contre Le Cancer, 31037, Toulouse, France

    Fatima Bilal, Michaël Pérès, Nathalie Andrieu-Abadie, Thierry Levade & Bruno Ségui

  3. Université Libanaise, Ecole Doctorale de Sciences et Technologies, Campus Universitaire de Rafic Hariri, Hadath, Lebanon

    Fatima Bilal, Bassam Badran & Ahmad Daher

  4. Université Toulouse III—Paul Sabatier, 118 route de Narbonne, 31062, Toulouse, France

    Fatima Bilal, Thierry Levade & Bruno Ségui

  5. Laboratoire de Biochimie, Institut Fédératif de Biologie, CHU Purpan, 31059, Toulouse, France

    Thierry Levade

Authors
  1. Fatima Bilal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michaël Pérès
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nathalie Andrieu-Abadie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thierry Levade
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bassam Badran
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ahmad Daher
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bruno Ségui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bruno Ségui .

Editor information

Editors and Affiliations

  1. INSERM, LNC UMR 1231, Dijon, France

    Olivier Micheau

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Bilal, F. et al. (2017). Role of Sphingolipids in Death Receptor Signalling. In: Micheau, O. (eds) TRAIL, Fas Ligand, TNF and TLR3 in Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-56805-8_10

Download citation

Publish with us

Policies and ethics

Search

Navigation