Skip to main content

Advertisement

SpringerLink
Log in

Intracellular localization of DR5 and related regulatory pathways as a mechanism of resistance to TRAIL in cancer

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

TNF-related apoptosis-inducing ligand (TRAIL) is a prominent cytokine capable of inducing apoptosis. It can bind to five different cognate receptors, through which diverse intracellular pathways can be activated. TRAIL’s ability to preferentially kill transformed cells makes it a promising potential weapon for targeted tumor therapy. However, recognition of several resistance mechanisms to TRAIL-induced apoptosis has indicated that a thorough understanding of the details of TRAIL biology is still essential before this weapon can be confidently unleashed. Critical to this aim is revealing the functions and regulation mechanisms of TRAIL’s potent death receptor DR5. Although expression and signaling mechanisms of DR5 have been extensively studied, other aspects, such as its subcellular localization, non-signaling functions, and regulation of its membrane transport, have only recently attracted attention. Here, we discuss different aspects of TRAIL/DR5 biology, with a particular emphasis on the factors that seem to influence the cell surface expression pattern of DR5, along with factors that lead to its nuclear localization. Disturbance of this balance apparently affects the sensitivity of cancer cells to TRAIL-mediated apoptosis, thus constituting an eligible target for potential new therapeutic agents.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AR:

Androgen receptor

BNIP3:

Bcl-2 19 kDa interacting protein

c-FLIP:

Cellular FLICE-like protein

DD:

Death domain

DED:

Death effector domain

ELAVL1:

Embryonic lethal abnormal vision-like RNA-binding protein 1

FADD:

FAD-associated death domain protein

FLICE:

FADD-like interleukin-1 beta-converting enzyme

HuR:

Human antigen R

NLS:

Nuclear localization signal

PDAC:

Pancreatic ductal adenocarcinoma cells

RIP1:

Receptor-interacting protein 1

SRP:

Signal recognition particle

TRAF2:

TNF receptor-associated factor 2

TRAIL:

TNF-related apoptosis-inducing ligand

TRAIL-R:

TRAIL receptors

UPS:

Ubiquitin-proteasome system

UDPL:

3′-UTR-dependent protein localization

YY1:

Yin Yang 1

References

  1. Wiley SR et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3(6):673–682

    Article  CAS  PubMed  Google Scholar 

  2. Gong B, Almasan A (2000) Genomic organization and transcriptional regulation of human Apo2/TRAIL gene. Biochem Biophys Res Commun 278(3):747–752

    Article  CAS  PubMed  Google Scholar 

  3. Harith HH, Morris MJ, Kavurma MM (2013) On the TRAIL of obesity and diabetes. Trends Endocrinol Metab 24(11):578–587

    Article  CAS  PubMed  Google Scholar 

  4. Audo R et al (2015) Osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand as prognostic factors in rheumatoid arthritis: results from the ESPOIR cohort. Arthritis Res Ther 17:193

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. de Miguel D et al (2016) Onto better TRAILs for cancer treatment. Cell Death Differ 23(5):733–747

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Di Bartolo BA et al (2011) TNF-related apoptosis-inducing ligand (TRAIL) protects against diabetes and atherosclerosis in Apoe/mice. Diabetologia 54(12):3157–3167

    Article  CAS  PubMed  Google Scholar 

  7. Huang Y et al (2005) The role of TNF related apoptosis-inducing ligand in neurodegenerative diseases. Cell Mol Immunol 2(2):113–122

    CAS  PubMed  Google Scholar 

  8. Hilliard B et al (2001) Roles of TNF-related apoptosis-inducing ligand in experimental autoimmune encephalomyelitis. J Immunol 166(2):1314–1319

    Article  CAS  PubMed  Google Scholar 

  9. Pan G et al (1997) The receptor for the cytotoxic ligand TRAIL. Science 276(5309):111–113

    Article  CAS  PubMed  Google Scholar 

  10. Walczak H et al (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 16(17):5386–5397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Falschlehner C et al (2007) TRAIL signalling: decisions between life and death. Int J Biochem Cell Biol 39(7–8):1462–1475

    Article  CAS  PubMed  Google Scholar 

  12. Degli-Esposti MA et al (1997) Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 186(7):1165–1170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Degli-Esposti MA et al (1997) The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 7(6):813–820

    Article  CAS  PubMed  Google Scholar 

  14. Emery JG et al (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273(23):14363–14367

    Article  CAS  PubMed  Google Scholar 

  15. Sanlioglu AD et al (2009) High TRAIL death receptor 4 and decoy receptor 2 expression correlates with significant cell death in pancreatic ductal adenocarcinoma patients. Pancreas 38(2):154–160

    Article  CAS  PubMed  Google Scholar 

  16. Koksal IT et al (2008) Tumor necrosis factor-related apoptosis inducing ligand-R4 decoy receptor expression is correlated with high Gleason scores, prostate-specific antigen recurrence, and decreased survival in patients with prostate carcinoma. Urol Oncol 26(2):158–165

    Article  CAS  PubMed  Google Scholar 

  17. Walczak H et al (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5(2):157–163

    Article  CAS  PubMed  Google Scholar 

  18. Ashkenazi A et al (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Investig 104(2):155–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bellail AC et al (2009) TRAIL agonists on clinical trials for cancer therapy: the promises and the challenges. Rev Recent Clin Trials 4(1):34–41

    Article  CAS  PubMed  Google Scholar 

  20. Mirandola P et al (2004) Activated human NK and CD8+ T cells express both TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors but are resistant to TRAIL-mediated cytotoxicity. Blood 104(8):2418–2424

    Article  CAS  PubMed  Google Scholar 

  21. Meurette O et al (2005) TRAIL (TNF-related apoptosis-inducing ligand) induces necrosis-like cell death in tumor cells at acidic extracellular pH. Ann N Y Acad Sci 1056:379–387

    Article  CAS  PubMed  Google Scholar 

  22. Zhang L, Fang B (2005) Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther 12(3):228–237

    Article  CAS  PubMed  Google Scholar 

  23. Hymowitz SG et al (2000) A unique zinc-binding site revealed by a high-resolution X-ray structure of homotrimeric Apo2L/TRAIL. Biochemistry 39(4):633–640

    Article  CAS  PubMed  Google Scholar 

  24. Walczak H, Haas TL (2008) Biochemical analysis of the native TRAIL death-inducing signaling complex. Methods Mol Biol 414:221–239

    CAS  PubMed  Google Scholar 

  25. Bodmer JL et al (2000) TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol 2(4):241–243

    Article  CAS  PubMed  Google Scholar 

  26. Dickens LS et al (2012) A death effector domain chain DISC model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol Cell 47(2):291–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pennarun B et al (2010) Playing the DISC: turning on TRAIL death receptor-mediated apoptosis in cancer. Biochim Biophys Acta 1805(2):123–140

    CAS  PubMed  Google Scholar 

  28. Song JH et al (2007) 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 67(14):6946–6955

    Article  CAS  PubMed  Google Scholar 

  29. Huang K et al (2016) Cleavage by caspase 8 and mitochondrial membrane association activate bid during TRAIL-induced apoptosis. J Biol Chem 291(22):11843–11851

    Article  CAS  PubMed  Google Scholar 

  30. Lee DH et al (2016) TRAIL-induced caspase activation is a prerequisite for activation of the endoplasmic reticulum stress-induced signal transduction pathways. J Cell Biochem 117(5):1078–1091

    Article  CAS  PubMed  Google Scholar 

  31. Varfolomeev E et al (2005) Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J Biol Chem 280(49):40599–40608

    Article  CAS  PubMed  Google Scholar 

  32. Azijli K et al (2013) Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family. Cell Death Differ 20(7):858–868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Krueger A et al (2001) FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 21(24):8247–8254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Aydin C et al (2007) Decoy receptor-2 small interfering RNA (siRNA) strategy employing three different siRNA constructs in combination defeats adenovirus-transferred tumor necrosis factor-related apoptosis-inducing ligand resistance in lung cancer cells. Hum Gene Ther 18(1):39–50

    Article  CAS  PubMed  Google Scholar 

  35. Sanlioglu AD et al (2006) Adenovirus-mediated IKKbetaKA expression sensitizes prostate carcinoma cells to TRAIL-induced apoptosis. Cancer Gene Ther 13(1):21–31

    Article  CAS  PubMed  Google Scholar 

  36. Trivedi R, Mishra DP (2015) Trailing TRAIL resistance: novel targets for TRAIL sensitization in cancer cells. Front Oncol 5:69

    Article  PubMed  PubMed Central  Google Scholar 

  37. O’Leary L et al (2016) Decoy receptors block TRAIL sensitivity at a supracellular level: the role of stromal cells in controlling tumour TRAIL sensitivity. Oncogene 35(10):1261–1270

    Article  PubMed  CAS  Google Scholar 

  38. Chaudhary PM et al (1997) Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Immunity 7(6):821–830

    Article  CAS  PubMed  Google Scholar 

  39. Kelley RF et al (2005) Receptor-selective mutants of apoptosis-inducing ligand 2/tumor necrosis factor-related apoptosis-inducing ligand reveal a greater contribution of death receptor (DR) 5 than DR4 to apoptosis signaling. J Biol Chem 280(3):2205–2212

    Article  CAS  PubMed  Google Scholar 

  40. LeBlanc HN, Ashkenazi A (2003) Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 10(1):66–75

    Article  CAS  PubMed  Google Scholar 

  41. Truneh A et al (2000) Temperature-sensitive differential affinity of TRAIL for its receptors. DR5 is the highest affinity receptor. J Biol Chem 275(30):23319–23325

    Article  CAS  PubMed  Google Scholar 

  42. Wu GS et al (1997) KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet 17(2):141–143

    Article  CAS  PubMed  Google Scholar 

  43. Yamaguchi H, Wang HG (2004) CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem 279(44):45495–45502

    Article  CAS  PubMed  Google Scholar 

  44. Yoshida T et al (2005) Proteasome inhibitor MG132 induces death receptor 5 through CCAAT/enhancer-binding protein homologous protein. Cancer Res 65(13):5662–5667

    Article  CAS  PubMed  Google Scholar 

  45. Kouhara J et al (2007) Fenretinide up-regulates DR5/TRAIL-R2 expression via the induction of the transcription factor CHOP and combined treatment with fenretinide and TRAIL induces synergistic apoptosis in colon cancer cell lines. Int J Oncol 30(3):679–687

    CAS  PubMed  Google Scholar 

  46. Oh YT et al (2010) ERK/ribosomal S6 kinase (RSK) signaling positively regulates death receptor 5 expression through co-activation of CHOP and Elk1. J Biol Chem 285(53):41310–41319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Eckhardt I, Roesler S, Fulda S (2013) Identification of DR5 as a critical, NF-kappaB-regulated mediator of Smac-induced apoptosis. Cell Death Dis 4:e936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chen JJ et al (2008) Proteasome inhibitors enhance TRAIL-induced apoptosis through the intronic regulation of DR5: involvement of NF-kappa B and reactive oxygen species-mediated p53 activation. J Immunol 180(12):8030–8039

    Article  CAS  PubMed  Google Scholar 

  49. Zou W et al (2004) c-Jun NH2-terminal kinase-mediated up-regulation of death receptor 5 contributes to induction of apoptosis by the novel synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1, 9-dien-28-oate in human lung cancer cells. Cancer Res 64(20):7570–7578

    Article  CAS  PubMed  Google Scholar 

  50. Higuchi H et al (2004) Bile acids up-regulate death receptor 5/TRAIL-receptor 2 expression via a c-Jun N-terminal kinase-dependent pathway involving Sp1. J Biol Chem 279(1):51–60

    Article  CAS  PubMed  Google Scholar 

  51. Chen Q et al (2010) Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells. PLoS One 5(12):e15288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Baritaki S et al (2007) Regulation of tumor cell sensitivity to TRAIL-induced apoptosis by the metastatic suppressor Raf kinase inhibitor protein via Yin Yang 1 inhibition and death receptor 5 up-regulation. J Immunol 179(8):5441–5453

    Article  CAS  PubMed  Google Scholar 

  53. Burton TR et al (2013) BNIP3 acts as transcriptional repressor of death receptor-5 expression and prevents TRAIL-induced cell death in gliomas. Cell Death Dis 4:e587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Gerstein MB et al (2012) Architecture of the human regulatory network derived from ENCODE data. Nature 489(7414):91–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Koksal IT et al (2010) Effects of androgen ablation therapy in TRAIL death ligand and its receptors expression in advanced prostate cancer. Urol Int 84(4):445–451

    Article  CAS  PubMed  Google Scholar 

  56. Massie CE et al (2007) New androgen receptor genomic targets show an interaction with the ETS1 transcription factor. EMBO Rep 8(9):871–878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Todo M et al (2013) Ibuprofen enhances TRAIL-induced apoptosis through DR5 upregulation. Oncol Rep 30(5):2379–2384

    CAS  PubMed  Google Scholar 

  58. Taniguchi H et al (2008) Baicalein overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance via two different cell-specific pathways in cancer cells but not in normal cells. Cancer Res 68(21):8918–8927

    Article  CAS  PubMed  Google Scholar 

  59. Prasad S et al (2014) Targeting death receptors for TRAIL by agents designed by Mother Nature. Trends Pharmacol Sci 35(10):520–536

    Article  CAS  PubMed  Google Scholar 

  60. Wong N, Wang X (2015) miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 43(Database issue):D146–D152

    Article  PubMed  Google Scholar 

  61. Gerstberger S, Hafner M, Tuschl T (2014) A census of human RNA-binding proteins. Nat Rev Genet 15(12):829–845

    Article  CAS  PubMed  Google Scholar 

  62. Glisovic T et al (2008) RNA-binding proteins and post-transcriptional gene regulation. FEBS Lett 582(14):1977–1986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Yang YC et al (2015) CLIPdb: a CLIP-seq database for protein-RNA interactions. BMC Genom 16:51

    Article  CAS  Google Scholar 

  64. Wang W et al (2000) HuR regulates p21 mRNA stabilization by UV light. Mol Cell Biol 20(3):760–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Blaxall BC et al (2000) Purification and characterization of beta-adrenergic receptor mRNA-binding proteins. J Biol Chem 275(6):4290–4297

    Article  CAS  PubMed  Google Scholar 

  66. Goldberg-Cohen I, Furneauxb H, Levy AP (2002) A 40-bp RNA element that mediates stabilization of vascular endothelial growth factor mRNA by HuR. J Biol Chem 277(16):13635–13640

    Article  CAS  PubMed  Google Scholar 

  67. Yeap BB et al (2002) Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif within the 3′-untranslated region of the androgen receptor messenger RNA. J Biol Chem 277(30):27183–27192

    Article  CAS  PubMed  Google Scholar 

  68. Fan XC, Steitz JA (1998) HNS, a nuclear-cytoplasmic shuttling sequence in HuR. Proc Natl Acad Sci USA 95(26):15293–15298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fan XC, Steitz JA (1998) Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. EMBO J 17(12):3448–3460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Brennan CM, Steitz JA (2001) HuR and mRNA stability. Cell Mol Life Sci 58(2):266–277

    Article  CAS  PubMed  Google Scholar 

  71. Takeuchi O (2015) HuR keeps interferon-beta mRNA stable. Eur J Immunol 45(5):1296–1299

    Article  CAS  PubMed  Google Scholar 

  72. Kandasamy K, Kraft AS (2008) Proteasome inhibitor PS-341 (VELCADE) induces stabilization of the TRAIL receptor DR5 mRNA through the 3′-untranslated region. Mol Cancer Ther 7(5):1091–1100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Pineda DM et al (2012) HuR’s post-transcriptional regulation of Death Receptor 5 in pancreatic cancer cells. Cancer Biol Ther 13(10):946–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Schabath MB et al (2013) TNFRSF10B polymorphisms and haplotypes associated with increased risk of death in non-small cell lung cancer. Carcinogenesis 34(11):2525–2530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kriegl L et al (2012) Microsatellite instability, KRAS mutations and cellular distribution of TRAIL-receptors in early stage colorectal cancer. PLoS One 7(12):e51654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Jin Z et al (2004) Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 279(34):35829–35839

    Article  CAS  PubMed  Google Scholar 

  77. Spierings DC et al (2003) Expression of TRAIL and TRAIL death receptors in stage III non-small cell lung cancer tumors. Clin Cancer Res 9(9):3397–3405

    CAS  PubMed  Google Scholar 

  78. Sanlioglu AD et al (2007) Differential expression of TRAIL and its receptors in benign and malignant prostate tissues. J Urol 177(1):359–364

    Article  PubMed  Google Scholar 

  79. Ganten TM et al (2009) Prognostic significance of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor expression in patients with breast cancer. J Mol Med (Berl) 87(10):995–1007

    Article  CAS  Google Scholar 

  80. Bertsch U et al (2014) Compartmentalization of TNF-related apoptosis-inducing ligand (TRAIL) death receptor functions: emerging role of nuclear TRAIL-R2. Cell Death Dis 5:e1390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Carpenter G, Liao HJ (2009) Trafficking of receptor tyrosine kinases to the nucleus. Exp Cell Res 315(9):1556–1566

    Article  CAS  PubMed  Google Scholar 

  82. Bryant DM, Stow JL (2005) Nuclear translocation of cell-surface receptors: lessons from fibroblast growth factor. Traffic 6(10):947–954

    Article  CAS  PubMed  Google Scholar 

  83. Kasuga K et al (2007) Generation of intracellular domain of insulin receptor tyrosine kinase by gamma-secretase. Biochem Biophys Res Commun 360(1):90–96

    Article  CAS  PubMed  Google Scholar 

  84. Kojima Y et al (2011) Importin beta1 protein-mediated nuclear localization of death receptor 5 (DR5) limits DR5/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death of human tumor cells. J Biol Chem 286(50):43383–43393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Haselmann V et al (2014) Nuclear death receptor TRAIL-R2 inhibits maturation of let-7 and promotes proliferation of pancreatic and other tumor cells. Gastroenterology 146(1):278–290

    Article  CAS  PubMed  Google Scholar 

  86. Ren YG et al (2004) Differential regulation of the TRAIL death receptors DR4 and DR5 by the signal recognition particle. Mol Biol Cell 15(11):5064–5074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Twomey JD et al (2015) Spatial dynamics of TRAIL death receptors in cancer cells. Drug Resist Updat 19:13–21

    Article  PubMed  Google Scholar 

  88. Schneider-Brachert W, Heigl U, Ehrenschwender M (2013) Membrane trafficking of death receptors: implications on signalling. Int J Mol Sci 14(7):14475–14503

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Yoshida T et al (2009) Repeated treatment with subtoxic doses of TRAIL induces resistance to apoptosis through its death receptors in MDA-MB-231 breast cancer cells. Mol Cancer Res 7(11):1835–1844

    Article  CAS  PubMed  Google Scholar 

  90. Horinaka M et al (2006) The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand. Mol Cancer Ther 5(4):945–951

    Article  CAS  PubMed  Google Scholar 

  91. Di X et al (2013) Accumulation of autophagosomes in breast cancer cells induces TRAIL resistance through downregulation of surface expression of death receptors 4 and 5. Oncotarget 4(9):1349–1364

    Article  PubMed  PubMed Central  Google Scholar 

  92. Liu GC et al (2009) Detachment of esophageal carcinoma cells from extracellular matrix causes relocalization of death receptor 5 and apoptosis. World J Gastroenterol 15(7):836–844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Grosse-Wilde A et al (2008) TRAIL-R deficiency in mice enhances lymph node metastasis without affecting primary tumor development. J Clin Investig 118(1):100–110

    Article  CAS  PubMed  Google Scholar 

  94. Goldberg GS et al (2001) Global effects of anchorage on gene expression during mammary carcinoma cell growth reveal role of tumor necrosis factor-related apoptosis-inducing ligand in anoikis. Cancer Res 61(4):1334–1337

    CAS  PubMed  Google Scholar 

  95. Lane D et al (2008) Cell detachment modulates TRAIL resistance in ovarian cancer cells by downregulating the phosphatidylinositol 3-kinase/Akt pathway. Int J Gynecol Cancer 18(4):670–676

    Article  CAS  PubMed  Google Scholar 

  96. Trauzold A et al (2006) TRAIL promotes metastasis of human pancreatic ductal adenocarcinoma. Oncogene 25(56):7434–7439

    Article  CAS  PubMed  Google Scholar 

  97. Ishimura N et al (2006) Trail induces cell migration and invasion in apoptosis-resistant cholangiocarcinoma cells. Am J Physiol Gastrointest Liver Physiol 290(1):G129–G136

    Article  CAS  PubMed  Google Scholar 

  98. Hoogwater FJ et al (2010) Oncogenic K-Ras turns death receptors into metastasis-promoting receptors in human and mouse colorectal cancer cells. Gastroenterology 138(7):2357–2367

    Article  CAS  PubMed  Google Scholar 

  99. Malin D et al (2011) Enhanced metastasis suppression by targeting TRAIL receptor 2 in a murine model of triple-negative breast cancer. Clin Cancer Res 17(15):5005–5015

    Article  CAS  PubMed  Google Scholar 

  100. von Karstedt S et al (2015) Cancer cell-autonomous TRAIL-R signaling promotes KRAS-driven cancer progression, invasion, and metastasis. Cancer Cell 27(4):561–573

    Article  CAS  Google Scholar 

  101. Kozik P et al (2010) A screen for endocytic motifs. Traffic 11(6):843–855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Akazawa Y et al (2009) Death receptor 5 internalization is required for lysosomal permeabilization by TRAIL in malignant liver cell lines. Gastroenterology 136(7):2365–2376 e1–e7

  103. Kohlhaas SL et al (2007) Receptor-mediated endocytosis is not required for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. J Biol Chem 282(17):12831–12841

    Article  CAS  PubMed  Google Scholar 

  104. Zhang Y, Zhang B (2008) TRAIL resistance of breast cancer cells is associated with constitutive endocytosis of death receptors 4 and 5. Mol Cancer Res 6(12):1861–1871

    Article  CAS  PubMed  Google Scholar 

  105. Zhang Y, Yoshida T, Zhang B (2009) TRAIL induces endocytosis of its death receptors in MDA-MB-231 breast cancer cells. Cancer Biol Ther 8(10):917–922

    Article  CAS  PubMed  Google Scholar 

  106. Austin CD et al (2006) Death-receptor activation halts clathrin-dependent endocytosis. Proc Natl Acad Sci USA 103(27):10283–10288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Song JJ et al (2010) c-Cbl-mediated degradation of TRAIL receptors is responsible for the development of the early phase of TRAIL resistance. Cell Signal 22(3):553–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. van de Kooij B et al (2013) Ubiquitination by the membrane-associated RING-CH-8 (MARCH-8) ligase controls steady-state cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor 1. J Biol Chem 288(9):6617–6628

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Liu X et al (2007) The proteasome inhibitor PS-341 (bortezomib) up-regulates DR5 expression leading to induction of apoptosis and enhancement of TRAIL-induced apoptosis despite up-regulation of c-FLIP and survivin expression in human NSCLC cells. Cancer Res 67(10):4981–4988

    Article  CAS  PubMed  Google Scholar 

  110. Lee YJ et al (2011) Inhibition of the ubiquitin-proteasome system sensitizes TRAIL-resistant prostate cancer cells by up-regulation of death receptor 5. Mol Med Rep 4(6):1255–1259

    CAS  PubMed  Google Scholar 

  111. Sarhan D, D’Arcy P, Lundqvist A (2014) Regulation of TRAIL-receptor expression by the ubiquitin-proteasome system. Int J Mol Sci 15(10):18557–18573

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Wagner KW et al (2007) Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 13(9):1070–1077

    Article  CAS  PubMed  Google Scholar 

  113. Wu YH et al (2012) Removal of syndecan-1 promotes TRAIL-induced apoptosis in myeloma cells. J Immunol 188(6):2914–2921

    Article  CAS  PubMed  Google Scholar 

  114. Chen JJ et al (2014) H-Ras regulation of TRAIL death receptor mediated apoptosis. Oncotarget 5(13):5125–5137

    Article  PubMed  PubMed Central  Google Scholar 

  115. Chen JJ et al (2013) TRAIL induces apoptosis in oral squamous carcinoma cells—a crosstalk with oncogenic Ras regulated cell surface expression of death receptor 5. Oncotarget 4(2):206–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Psahoulia FH et al (2007) Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Mol Cancer Ther 6(9):2591–2599

    Article  CAS  PubMed  Google Scholar 

  117. Yan S et al (2014) Bufalin enhances TRAIL-induced apoptosis by redistributing death receptors in lipid rafts in breast cancer cells. Anticancer Drugs 25(6):683–689

    CAS  PubMed  Google Scholar 

  118. Tholanikunnel BG et al (2010) Novel mechanisms in the regulation of G protein-coupled receptor trafficking to the plasma membrane. J Biol Chem 285(44):33816–33825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Berkovits BD, Mayr C (2015) Alternative 3′ UTRs act as scaffolds to regulate membrane protein localization. Nature 522(7556):363–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Grosse-Wilde A, Kemp CJ (2008) Metastasis suppressor function of tumor necrosis factor-related apoptosis-inducing ligand-R in mice: implications for TRAIL-based therapy in humans? Cancer Res 68(15):6035–6037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Fritsche H et al (2015) TRAIL-R2 promotes skeletal metastasis in a breast cancer xenograft mouse model. Oncotarget 6(11):9502–9516

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the Research Fund of Akdeniz University, Project Number TDK-2015-942.

Author information

Authors and Affiliations

  1. Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, 07058, Antalya, Turkey

    Ufuk Mert & Ahter Dilsad Sanlioglu

  2. Center for Gene and Cell Therapy, Akdeniz University, 07058, Antalya, Turkey

    Ahter Dilsad Sanlioglu

Authors
  1. Ufuk Mert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahter Dilsad Sanlioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahter Dilsad Sanlioglu.

Ethics declarations

Conflict of interest

The authors declare no conflict of interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mert, U., Sanlioglu, A.D. Intracellular localization of DR5 and related regulatory pathways as a mechanism of resistance to TRAIL in cancer. Cell. Mol. Life Sci. 74, 245–255 (2017). https://doi.org/10.1007/s00018-016-2321-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-016-2321-z

Keywords

Search

Navigation