Vol 10, No 3 (2019)
Review paper
Published online: 2019-12-20

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Mechanism of activity and defensive strategies of cancer cells against TRAIL-induced apoptosis

Karolina Piechna1, Przemysław Juszczyński1
Hematologia 2019;10(3):135-147.

Abstract

TRAIL (TNF-related apoptosis inducing ligand), a protein belonging to the tumor necrosis factor family, causes apoptosis induction through activation of its cognate death receptors (DR4, DR5). Binding TRAIL leads to induction of extrinsic or, in some cell types, intrinsic apoptosis pathways. Because of the lower death receptors surface expression on non-transformed cells than on cancer cells, DR4 and DR5 ligands attract a lot of attention as potential anti-cancer drugs. Despite exhibiting high activity in preclinical in vitro and in vivo models, in clinical trials TRAIL treatment proved to be inefficient. Lack of apoptotic activity is caused by intrinsic or secondary resistance to TRAIL, that is observed in cancer cells. Herein, we systematically review the resistance mechanisms to death-receptor triggered apoptosis. Identification of such mechanisms in clinical setting might serve as a “negative” biomarker, excluding patients unlikely to benefit from TRAIL-based therapies or present a possibility of pharmacological modulation.

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References

  1. Nicholson DW. From bench to clinic with apoptosis-based therapeutic agents. Nature. 2000; 407(6805): 810–816.
  2. Wei MC, Zong WX, Cheng EH, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 2001; 292(5517): 727–730.
  3. Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer. 2002; 2(6): 420–430.
  4. Ogasawara J, Watanabe-Fukunaga R, Adachi M, et al. Lethal effect of the anti-Fas antibody in mice. Nature. 1993; 364(6440): 806–809.
  5. Kimura K, Taguchi T, Urushizaki I, et al. Phase I study of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol. 1987; 20(3): 223–229.
  6. Wiley SR, Schooley K, Smolak P, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995; 3(6): 673–682.
  7. Pitti RM, Marsters SA, Ruppert S, et al. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem. 1996; 271(22): 12687–12690.
  8. Sheridan JP, Marsters SA, Pitti RM, et al. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science. 1997; 277(5327): 818–821.
  9. Armitage RJ. Tumor necrosis factor receptor superfamily members and their ligands. Curr Opin Immunol. 1994; 6(3): 407–413.
  10. Pan G, O'Rourke K, Chinnaiyan AM, et al. The receptor for the cytotoxic ligand TRAIL. Science. 1997; 276(5309): 111–113.
  11. Walczak H. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J. 1997; 16(17): 5386–5397.
  12. Degli-Esposti MA, Smolak PJ, Walczak H, et al. Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med. 1997; 186(7): 1165–1170.
  13. Degli-Esposti MA, Dougall WC, Smolak PJ, et al. The novel receptor TRAIL-R4 induces NF-κB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity. 1997; 7(6): 813–820.
  14. Van Antwerp DJ, Martin SJ, Kafri T, et al. Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science. 1996; 274(5288): 787–789.
  15. Wajant H, Pfizenmaier K, Scheurich P. TNF-related apoptosis inducing ligand (TRAIL) and its receptors in tumor surveillance and cancer therapy. Apoptosis. 2002; 7(5): 449–459.
  16. Emery JG, McDonnell P, Burke MB, et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem. 1998; 273(23): 14363–14367.
  17. Boldin MP, Goncharov TM, Goltseve YV, et al. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell. 1996; 85(6): 803–815.
  18. Boldin MP, Varfolomeev EE, Pancer Z, et al. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain. J Biol Chem. 1995; 270(14): 7795–7798.
  19. Kischkel FC, Lawrence DA, Tinel A, et al. Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8. J Biol Chem. 2001; 276(49): 46639–46646.
  20. Kischkel FC, Hellbardt S, Behrmann I, et al. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J. 1995; 14(22): 5579–5588.
  21. Stennicke HR, Jürgensmeier JM, Shin H, et al. Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem. 1998; 273(42): 27084–27090.
  22. Jost PJ, Grabow S, Gray D, et al. XIAP discriminates between type I and type II FAS-induced apoptosis. Nature. 2009; 460(7258): 1035–1039.
  23. Li H, Zhu H, Xu Cj, et al. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998; 94(4): 491–501.
  24. Lindsten T, Ross A, King A, et al. The combined functions of proapoptotic Bcl-2 family members Bak and Bax are essential for normal development of multiple tissues. Mol Cell. 2000; 6(6): 1389–1399.
  25. Arnoult D, Gaume B, Karbowski M, et al. Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax/Bak-mediated permeabilization. EMBO J. 2003; 22(17): 4385–4399.
  26. Li K, Li Y, Shelton J, et al. Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell. 2000; 101(4): 389–399.
  27. Zou H, Li Y, Liu X, et al. An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem. 1999; 274(17): 11549–11556.
  28. Boatright KM, Scott FL, Sperandio S, et al. A unified model for apical caspase activation. Mol Cell. 2003; 11(2): 529–541.
  29. Du C, Fang M, Li Y, et al. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell. 2000; 102(1): 33–42.
  30. Suzuki Y, Imai Y, Nakayama H, et al. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell. 2001; 8(3): 613–621.
  31. Hunter AM, LaCasse EC, Korneluk RG. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis. 2007; 12(9): 1543–1568.
  32. Kemp TJ, Kim JS, Crist SA, et al. Induction of necrotic tumor cell death by TRAIL/Apo-2L. Apoptosis. 2003; 8(6): 587–599.
  33. Mocarski ES, Upton JW, Kaiser WJ. Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways. Nat Rev Immunol. 2011; 12(2): 79–88.
  34. Festjens N, Vanden Berghe T, Vandenabeele P. Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta. 2006; 1757(9-10): 1371–1387.
  35. Cho YS, Challa S, Moquin D, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009; 137(6): 1112–1123.
  36. Li J, McQuade T, Siemer AB, et al. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell. 2012; 150(2): 339–350.
  37. Steller H. Mechanisms and genes of cellular suicide. Science. 1995; 267(5203): 1445–1449.
  38. Zhao J, Jitkaew S, Cai Z, et al. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci USA. 2012; 109(14): 5322–5327.
  39. Sun L, Wang H, Wang Z, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012; 148(1-2): 213–227.
  40. Dyer MJS, MacFarlane M, Cohen GM. Barriers to effective TRAIL-targeted therapy of malignancy. J Clin Oncol. 2007; 25(28): 4505–4506.
  41. MacFarlane M, Ahmad M, Srinivasula SM, et al. Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. J Biol Chem. 1997; 272(41): 25417–25420.
  42. Lee S, Shin M, Kim H, et al. Alterations of the DR5/TRAIL receptor 2 gene in non-small cell lung cancers. Cancer Res. 1999; 59(22): 5683–5686.
  43. Pai SI, Wu GS, Ozören N, et al. Rare loss-of-function mutation of a death receptor gene in head and neck cancer. Cancer Res. 1998; 58(16): 3513–3518.
  44. Lee SH, Shin MS, Kim HS, et al. Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma. Oncogene. 2001; 20(3): 399–403.
  45. Yoshida T, Maeda A, Tani N, et al. Promoter structure and transcription initiation sites of the human death receptor 5/TRAIL-R2 gene. FEBS Lett. 2001; 507(3): 381–385.
  46. Shetty S, Graham BA, Brown JG, et al. Transcription factor NF-kappaB differentially regulates death receptor 5 expression involving histone deacetylase 1. Mol Cell Biol. 2005; 25(13): 5404–5416.
  47. Wagner KW, King F, Nomoto K, et al. Activation and suppression of the TRAIL death-receptor pathway in chemotherapy sensitive and resistant follicular lymphoma cells. Cancer Biol Ther. 2003; 2(5): 534–540.
  48. Rosenwald A, Chuang EY, Davis RE, et al. Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response. Blood. 2004; 104(5): 1428–1434.
  49. Young KH, Weisenburger DD, Dave BJ, et al. Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma. Blood. 2007; 110(13): 4396–4405.
  50. Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 1996; 274(5288): 782–784.
  51. Zong WX, Edelstein LC, Chen C, et al. The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappaB that blocks TNFalpha-induced apoptosis. Genes Dev. 1999; 13(4): 382–387.
  52. Chen C, Edelstein LC, Gélinas C. The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol Cell Biol. 2000; 20(8): 2687–2695.
  53. Wang CY, Mayo MW, Korneluk RG, et al. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science. 1998; 281(5383): 1680–1683.
  54. Ryan KM, Ernst MK, Rice NR, et al. Role of NF-kappaB in p53-mediated programmed cell death. Nature. 2000; 404(6780): 892–897.
  55. Mendoza FJ, Ishdorj G, Hu X, et al. Death receptor-4 (DR4) expression is regulated by transcription factor NF-kappaB in response to etoposide treatment. Apoptosis. 2008; 13(6): 756–770.
  56. Ravi R, Bedi GC, Engstrom LW, et al. Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB. Nat Cell Biol. 2001; 3(4): 409–416.
  57. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011; 334(6059): 1081–1086.
  58. He Q, Lee DIk, Rong R, et al. Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway. Oncogene. 2002; 21(17): 2623–2633.
  59. Lim JH, Park JW, Choi KS, et al. Rottlerin induces apoptosis via death receptor 5 (DR5) upregulation through CHOP-dependent and PKC delta-independent mechanism in human malignant tumor cells. Carcinogenesis. 2009; 30(5): 729–736.
  60. Kim EH, Yoon MiJ, Kim SU, et al. Arsenic trioxide sensitizes human glioma cells, but not normal astrocytes, to TRAIL-induced apoptosis via CCAAT/enhancer-binding protein homologous protein-dependent DR5 up-regulation. Cancer Res. 2008; 68(1): 266–275.
  61. Seligson D, Horvath S, Huerta-Yepez S, et al. Expression of transcription factor Yin Yang 1 in prostate cancer. Cancer Res. 2005; 65(9 Suppl).
  62. Martínez-Paniagua MA, Baritaki S, Huerta-Yepez S, et al. Mcl-1 and YY1 inhibition and induction of DR5 by the BH3-mimetic Obatoclax (GX15-070) contribute in the sensitization of B-NHL cells to TRAIL apoptosis. Cell Cycle. 2011; 10(16): 2792–2805.
  63. Shirley S, Morizot A, Micheau O. Regulating TRAIL receptor-induced cell death at the membrane : a deadly discussion. Recent Pat Anticancer Drug Discov. 2011; 6(3): 311–323.
  64. Song JJ, Szczepanski MJ, Kim SoY, et al. c-Cbl-mediated degradation of TRAIL receptors is responsible for the development of the early phase of TRAIL resistance. Cell Signal. 2010; 22(3): 553–563.
  65. Sanjay A, Horne WC, Baron R. The Cbl family: ubiquitin ligases regulating signaling by tyrosine kinases. Sci STKE. 2001; 2001(110): pe40–pe40.
  66. Kim SY, Kim JH, Song JJ. c-Cbl shRNA-expressing adenovirus sensitizes TRAIL-induced apoptosis in prostate cancer DU-145 through increases of DR4/5. Cancer Gene Ther. 2013; 20(2): 82–87.
  67. Zhang Y, Zhang B. TRAIL resistance of breast cancer cells is associated with constitutive endocytosis of death receptors 4 and 5. Mol Cancer Res. 2008; 6(12): 1861–1871.
  68. Fauconnier J, Meli AC, Thireau J, et al. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion. Proc Natl Acad Sci USA. 2011; 108(32): 13258–13263.
  69. Reis CR, Chen PH, Bendris N, et al. TRAIL-death receptor endocytosis and apoptosis are selectively regulated by dynamin-1 activation. Proc Natl Acad Sci USA. 2017; 114(3): 504–509.
  70. Micheau O. Regulation of TNF-related apoptosis-inducing ligand signaling by glycosylation. Int J Mol Sci. 2018; 19(3).
  71. Wagner KW, Punnoose EA, Januario T, et al. Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med. 2007; 13(9): 1070–1077.
  72. Dufour F, Rattier T, Shirley S, et al. N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death. Cell Death Differ. 2017; 24(3): 500–510.
  73. Jung YH, Lim EJ, Heo J, et al. Tunicamycin sensitizes human prostate cells to TRAIL-induced apoptosis by upregulation of TRAIL receptors and downregulation of cIAP2. Int J Oncol. 2012; 40(6): 1941–1948.
  74. Zhang HY, Du ZX, Liu BQ, et al. Tunicamycin enhances TRAIL-induced apoptosis by inhibition of cyclin D1 and the subsequent downregulation of survivin. Exp Mol Med. 2009; 41(5): 362–369.
  75. MacFarlane M, Robinson GL, Cain K. Glucose — a sweet way to die: metabolic switching modulates tumor cell death. Cell Cycle. 2012; 11(21): 3919–3925.
  76. Marsters SA, Sheridan JP, Pitti RM, et al. A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biol. 1997; 7(12): 1003–1006.
  77. Pan G, Ni J, Wei YF, et al. An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science. 1997; 277(5327): 815–818.
  78. Sheikh MS, Huang Y, Fernandez-Salas EA, et al. The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract. Oncogene. 1999; 18(28): 4153–4159.
  79. Sanlioglu AD, Dirice E, Aydin C, et al. Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells. BMC Cancer. 2005; 5: 54.
  80. Horak P, Pils D, Haller G, et al. Contribution of epigenetic silencing of tumor necrosis factor-related apoptosis inducing ligand receptor 1 (DR4) to TRAIL resistance and ovarian cancer. Mol Cancer Res. 2005; 3(6): 335–343.
  81. Simons K, Vaz W. Model systems, lipid rafts, and cell membranes. Annu Rev Biophys Biomol Struct. 2004; 33(1): 269–295.
  82. Song JH, Tse MCL, Bellail A, et al. Lipid rafts and nonrafts mediate tumor necrosis factor related apoptosis-inducing ligand induced apoptotic and nonapoptotic signals in non small cell lung carcinoma cells. Cancer Res. 2007; 67(14): 6946–6955.
  83. Ouyang W, Yang C, Zhang S, et al. Absence of death receptor translocation into lipid rafts in acquired TRAIL-resistant NSCLC cells. Int J Oncol. 2013; 42(2): 699–711.
  84. Kuang AA, Diehl GE, Zhang J, et al. FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts. J Biol Chem. 2000; 275(33): 25065–25068.
  85. Golks A, Brenner D, Fritsch C, et al. c-FLIPR, a new regulator of death receptor-induced apoptosis. J Biol Chem. 2005; 280(15): 14507–14513.
  86. Tschopp J, Irmler M, Thome M. Inhibition of Fas death signals by FLIPs. Curr Opin Immunol. 1998; 10(5): 552–558.
  87. Griffith TS, Chin WA, Jackson GC, et al. Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J Immunol. 1998; 161(6): 2833–2840.
  88. Hernandez A, Wang QD, Schwartz SA, et al. Sensitization of human colon cancer cells to trail-mediated apoptosis. J Gastrointest Surg. 2001; 5(1): 56–65.
  89. Griffith TS, Fialkov JM, Scott DL, et al. Induction and regulation of tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand-mediated apoptosis in renal cell carcinoma. Cancer Res. 2002; 62(11): 3093–3099.
  90. Fulda S, Meyer E, Debatin KM. Inhibition of TRAIL-induced apoptosis by Bcl-2 overexpression. Oncogene. 2002; 21(15): 2283–2294.
  91. Geserick P, Drewniok C, Hupe M, et al. Suppression of cFLIP is sufficient to sensitize human melanoma cells to TRAIL- and CD95L-mediated apoptosis. Oncogene. 2008; 27(22): 3211–3220.
  92. Bellail AC, Tse MCL, Song JH, et al. DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas. J Cell Mol Med. 2010; 14(6A): 1303–1317.
  93. Cao X, Pobezinskaya YL, Morgan MJ, et al. The role of TRADD in TRAIL-induced apoptosis and signaling. FASEB J. 2011; 25(4): 1353–1358.
  94. Braun FK, Mathur R, Sehgal L, et al. Inhibition of methyltransferases accelerates degradation of cFLIP and sensitizes B-cell lymphoma cells to TRAIL-induced apoptosis. PLoS One. 2015; 10(3): e0117994.
  95. Duprez L, Bertrand MJM, Vanden Berghe T, et al. Intermediate domain of receptor-interacting protein kinase 1 (RIPK1) determines switch between necroptosis and RIPK1 kinase-dependent apoptosis. J Biol Chem. 2012; 287(18): 14863–14872.
  96. Sun J, Luo H, Nie W, et al. Protective effect of RIP and c-FLIP in preventing liver cancer cell apoptosis induced by TRAIL. Int J Clin Exp Pathol. 2015; 8(6): 6519–6525.
  97. Nesterov A, Lu X, Johnson M, et al. Elevated AKT activity protects the prostate cancer cell line LNCaP from TRAIL-induced apoptosis. J Biol Chem. 2001; 276(14): 10767–10774.
  98. Lopez J, Meier P. To fight or die - inhibitor of apoptosis proteins at the crossroad of innate immunity and death. Curr Opin Cell Biol. 2010; 22(6): 872–881.
  99. Miller LK. An exegesis of IAPs: salvation and surprises from BIR motifs. Trends Cell Biol. 1999; 9(8): 323–328.
  100. Bertrand MJM, Milutinovic S, Dickson KM, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008; 30(6): 689–700.
  101. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003; 114(2): 181–190.
  102. Meylan E, Tschopp J. The RIP kinases: crucial integrators of cellular stress. Trends Biochem Sci. 2005; 30(3): 151–159.
  103. Letai AG. Diagnosing and exploiting cancer's addiction to blocks in apoptosis. Nat Rev Cancer. 2008; 8(2): 121–132.
  104. Hinz S, Trauzold A, Boenicke L, et al. Bcl-XL protects pancreatic adenocarcinoma cells against CD95- and TRAIL-receptor-mediated apoptosis. Oncogene. 2000; 19(48): 5477–5486.
  105. Sinicrope FA, Penington RC, Tang XiM. Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis is inhibited by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human colon cancer cells. Clin Cancer Res. 2004; 10(24): 8284–8292.
  106. Clohessy JG, Zhuang J, de Boer J, et al. Mcl-1 interacts with truncated Bid and inhibits its induction of cytochrome c release and its role in receptor-mediated apoptosis. J Biol Chem. 2006; 281(9): 5750–5759.
  107. Ndozangue-Touriguine O, Sebbagh M, Mérino D, et al. A mitochondrial block and expression of XIAP lead to resistance to TRAIL-induced apoptosis during progression to metastasis of a colon carcinoma. Oncogene. 2008; 27(46): 6012–6022.
  108. Hata AN, Engelman JA, Faber AC. The BCL2 family: key mediators of the apoptotic response to targeted anticancer therapeutics. Cancer Discov. 2015; 5(5): 475–487.
  109. Baeuerle PA, Henkel T. Function and activation of NF-kappaB in the immune system. Annu Rev Immunol. 1994; 12(1): 141–179.
  110. Malinin NL, Boldin MP, Kovalenko AV, et al. MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature. 1997; 385(6616): 540–544.
  111. Anees M, Horak P, Schiefer AI, et al. The potential evasion of immune surveillance in mucosa associated lymphoid tissue lymphoma by DcR2-mediated up-regulation of nuclear factor-κB. Leuk Lymphoma. 2015; 56(5): 1440–1449.
  112. Fadeev RS, Solovieva ME, Slyadovskiy DA, et al. [Inhibition of NF-kB activation decreases resistance in acute myeloid leukemia cells to TRAIL-induced apoptosis in multicellular aggregates]. [Article in Russian]. Biofizika. 2015; 60(6): 1146–1150.
  113. Crowder RN, El-Deiry WS. Caspase-8 regulation of TRAIL-mediated cell death. Exp Oncol. 2012; 34(3): 160–164.
  114. Soung YH, Lee JW, Kim SY, et al. CASPASE-8 gene is inactivated by somatic mutations in gastric carcinomas. Cancer Res. 2005; 65(3): 815–821.
  115. Eggert A, Grotzer M, Zuzak T, et al. Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression. Med Pediatr Oncol. 2000; 35(6): 603–607, doi: 10.1002/1096-911x(20001201)35:6<603::aid-mpo24>3.0.co;2-1.
  116. Grotzer MA, Eggert A, Zuzak TJ, et al. Resistance to TRAIL-induced apoptosis in primitive neuroectodermal brain tumor cells correlates with a loss of caspase-8 expression. Oncogene. 2000; 19(40): 4604–4610.
  117. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324(5930): 1029–1033.
  118. Pradelli LA, Bénéteau M, Chauvin C, et al. Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation. Oncogene. 2010; 29(11): 1641–1652.
  119. Robinson GL, Dinsdale D, Macfarlane M, et al. Switching from aerobic glycolysis to oxidative phosphorylation modulates the sensitivity of mantle cell lymphoma cells to TRAIL. Oncogene. 2012; 31(48): 4996–5006.
  120. Pradelli LA, Bénéteau M, Chauvin C, et al. Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation. Oncogene. 2010; 29(11): 1641–1652.
  121. Salinas M, López-Valdaliso R, Martín D, et al. Inhibition of PKB/Akt1 by C2-ceramide involves activation of ceramide-activated protein phosphatase in PC12 cells. Mol Cell Neurosci. 2000; 15(2): 156–169.
  122. Nam SY, Amoscato AA, Lee YJ. Low glucose-enhanced TRAIL cytotoxicity is mediated through the ceramide-Akt-FLIP pathway. Oncogene. 2002; 21(3): 337–346.
  123. Kroemer G, Mariño G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010; 40(2): 280–293.
  124. Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014; 157(1): 65–75.
  125. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008; 132(1): 27–42.
  126. Rubinstein AD, Kimchi A. Life in the balance - a mechanistic view of the crosstalk between autophagy and apoptosis. J Cell Sci. 2012; 125(Pt 22): 5259–5268.
  127. Di Xu, Zhang G, Zhang Y, et al. Accumulation of autophagosomes in breast cancer cells induces TRAIL resistance through downregulation of surface expression of death receptors 4 and 5. Oncotarget. 2013; 4(9): 1349–1364.
  128. Hou W, Han J, Lu C, et al. Enhancement of tumor-TRAIL susceptibility by modulation of autophagy. Autophagy. 2008; 4(7): 940–943.



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