Leukemia Research
Volume 33, Issue 11 , Pages 1440-1447 , November 2009

ER–Golgi network—A future target for anti-cancer therapy

  • Donald Wlodkowic

      Affiliations

    • Department of Biological & Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK
    • Cytotech Consultancy, Edinburgh, UK
    • Corresponding Author InformationCorresponding author at: Department of Biological & Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK. Tel.: +44 0798 824 5512.
  • ,
  • Joanna Skommer

      Affiliations

    • Cytotech Consultancy, Edinburgh, UK
  • ,
  • Dagmara McGuinness

      Affiliations

    • Women's Reproductive Health Research Center, Medical Center North, Vanderbilt University, Nashville, TN, USA
  • ,
  • Chris Hillier

      Affiliations

    • Department of Biological & Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK
  • ,
  • Zbigniew Darzynkiewicz

      Affiliations

    • Brander Cancer Research Institute, New York Medical College, Valhalla, NY, USA

Received 26 March 2009 ,Revised 14 May 2009 ,Accepted 29 May 2009.

References 

  1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70
  2. Broker LE, Kruyt FA, Giaccone G. Cell death independent of caspases: a review. Clin Cancer Res. 2005;11(9):3155–3162
  3. Crighton D, Ryan KM. Splicing DNA-damage responses to tumour cell death. Biochim Biophys Acta. 2004;1705(1):3–15
  4. Meng XW, Lee SH, Kaufmann SH. Apoptosis in the treatment of cancer: a promise kept?. Curr Opin Cell Biol. 2006;18(6):668–676
  5. Lowe SW, Ruley HE, Jacks T, Housman DE. p53-Dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 1993;74(6):957–967
  6. Kaufmann SH, Gores GJ. Apoptosis in cancer: cause and cure. Bioessays. 2000;22(11):1007–1017
  7. Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin. 2005;55(3):178–194
  8. Leist M, Jaattela M. Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol. 2001;2(8):589–598
  9. Jaattela M. Programmed cell death: many ways for cells to die decently. Ann Med. 2002;34(6):480–488
  10. Lockshin RA, Zakeri Z. Programmed cell death and apoptosis: origins of the theory. Nat Rev Mol Cell Biol. 2001;2(7):545–550
  11. Okada H, Mak TW. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer. 2004;4(8):592–603
  12. Edinger AL, Thompson CB. Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 2004;16(6):663–669
  13. Abraham MC, Shaham S. Death without caspases, caspases without death. Trends Cell Biol. 2004;14(4):184–193
  14. Hail N, Carter BZ, Konopleva M, Andreeff M. Apoptosis effector mechanisms: a requiem performed in different keys. Apoptosis. 2006;11(6):889–904
  15. Levine B, Yuan J. Autophagy in cell death: an innocent convict?. J Clin Invest. 2005;115(10):2679–2688
  16. Kroemer G, Jaattela M. Lysosomes and autophagy in cell death control. Nat Rev Cancer. 2005;5(11):886–897
  17. Kim R. Recent advances in understanding the cell death pathways activated by anticancer therapy. Cancer. 2005;103(8):1551–1560
  18. Kim R, Emi M, Tanabe K. Role of mitochondria as the gardens of cell death. Cancer Chemother Pharmacol. 2006;57(5):545–553
  19. Ferri KF, Kroemer G. Organelle-specific initiation of cell death pathways. Nat Cell Biol. 2001;3(11):E255–E263
  20. Maag RS, Hicks SW, Machamer CE. Death from within: apoptosis and the secretory pathway. Curr Opin Cell Biol. 2003;15(4):456–461
  21. Momoi T. Caspases involved in ER stress-mediated cell death. J Chem Neuroanat. 2004;28(1-2):101–105
  22. Hicks SW, Machamer CE. Golgi structure in stress sensing and apoptosis. Biochim Biophys Acta. 2005;1744(3):406–414
  23. Szegezdi E, Logue SE, Gorman AM, Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 2006;7(9):880–885
  24. Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: the calcium–apoptosis link. Nat Rev Mol Cell Biol. 2003;4(7):552–565
  25. Scorrano L, Korsmeyer SJ. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem Biophys Res Commun. 2003;304(3):437–444
  26. Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science. 2003;300(5616):135–139
  27. Chipuk JE, Maurer U, Green DR, Schuler M. Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell. 2003;4(5):371–381
  28. Chipuk JE, Green DR. p53's believe it or not: lessons on transcription-independent death. J Clin Immunol. 2003;23(5):355–361
  29. Chipuk JE, Bouchier-Hayes L, Green DR. Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ. 2006;13(8):1396–1402
  30. Skommer J, Wlodkowic D, Deptala A. Larger than life: mitochondria and the Bcl-2 family. Leuk Res. 2007;31(March (3)):277–286
  31. Machamer CE. Golgi disassembly in apoptosis: cause or effect?. Trends Cell Biol. 2003;13(6):279–281
  32. Rutkowski DT, Kaufman RJ. A trip to the ER: coping with stress. Trends Cell Biol. 2004;14(1):20–28
  33. Walter L, Hajnoczky G. Mitochondria and endoplasmic reticulum: the lethal interorganelle cross-talk. J Bioenerg Biomembr. 2005;37(3):191–206
  34. Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2000;2(6):326–332
  35. Katayama T, Imaizumi K, Sato N, Miyoshi K, Kudo T, Hitomi J, et al. Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response. Nat Cell Biol. 1999;1(8):479–485
  36. Patil C, Walter P. Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals. Curr Opin Cell Biol. 2001;13(3):349–355
  37. McCullough KD, Martindale JL, Klotz LO, Aw TY, Holbrook NJ. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol. 2001;21(4):1249–1259
  38. Shiraishi T, Yoshida T, Nakata S, Horinaka M, Wakada M, Mizutani Y, et al. Tunicamycin enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human prostate cancer cells. Cancer Res. 2005;65(14):6364–6370
  39. Li J, Lee B, Lee AS. Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J Biol Chem. 2006;281(11):7260–7270
  40. Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, et al. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem. 2001;276(17):13935–13940
  41. Urano F, Bertolotti A, Ron D. IRE1 and efferent signaling from the endoplasmic reticulum. J Cell Sci. 2000;113(Pt 21):3697–3702
  42. Bassik MC, Scorrano L, Oakes SA, Pozzan T, Korsmeyer SJ. Phosphorylation of BCL-2 regulates ER Ca2+ homeostasis and apoptosis. EMBO J. 2004;23(5):1207–1216
  43. Lei K, Davis RJ. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci USA. 2003;100(5):2432–2437
  44. van de Craen M, Vandenabeele P, Declercq W, Van den Brande I, Van Loo G, Molemans F, et al. Characterization of seven murine caspase family members. FEBS Lett. 1997;403(1):61–69
  45. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, et al. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 2000;403(6765):98–103
  46. Nakagawa T, Yuan J. Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol. 2000;150(4):887–894
  47. Liu H, Baliga R. Endoplasmic reticulum stress-associated caspase 12 mediates cisplatin-induced LLC-PK1 cell apoptosis. J Am Soc Nephrol. 2005;16:1985–1992
  48. Morishima N, Nakanishi K, Takenouchi H, Shibata T, Yasuhiko Y. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J Biol Chem. 2002;277(37):34287–34294
  49. Fischer H, Koenig U, Eckhart L, Tschachler E. Human caspase 12 has acquired deleterious mutations. Biochem Biophys Res Commun. 2002;293(2):722–726
  50. Hitomi J, Katayama T, Eguchi Y, Kudo T, Taniguchi M, Koyama Y, et al. Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death. J Cell Biol. 2004;165(3):347–356
  51. Breckenridge DG, Nguyen M, Kuppig S, Reth M, Shore GC. The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum. Proc Natl Acad Sci USA. 2002;99(7):4331–4336
  52. Thomenius MJ, Distelhorst CW. Bcl-2 on the endoplasmic reticulum: protecting the mitochondria from a distance. J Cell Sci. 2003;116(Pt 22):4493–4499
  53. Chen R, Valencia I, Zhong F, McColl KS, Roderick HL, Bootman MD, et al. Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J Cell Biol. 2004;166(2):193–203
  54. Mannella CA, Buttle K, Rath BK, Marko M. Electron microscopic tomography of rat-liver mitochondria and their interaction with the endoplasmic reticulum. Biofactors. 1998;8(3-4):225–228
  55. Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, et al. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science. 1998;280(5370):1763–1766
  56. Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH. Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nat Cell Biol. 2003;5(12):1051–1061
  57. Guicciardi ME, Gores GJ. Calpains can do it alone: implications for cancer therapy. Cancer Biol Ther. 2003;2(2):153–154
  58. Sesso A, Fujiwara DT, Jaeger M, Jaeger R, Li TC, Monteiro MM, et al. Structural elements common to mitosis and apoptosis. Tissue Cell. 1999;31(3):357–371
  59. Ruan Q, Wang Q, Xie S, Fang Y, Darzynkiewicz Z, Guan K, et al. Polo-like kinase 3 is Golgi localized and involved in regulation of Golgi fragmentation during the cell cycle. Exp Cell Res. 2004;294:51–59
  60. Jiang N, Wang X, Jhanwar-Uniyal M, Darzynkiewicz Z, Dai W. Polo box domain of Plk3 functions as a centrosome localization signal, overexpression of which causes mitotic arrest, cytokinesis defects, and apoptosis. J Biol Chem. 2006;281:10577–10582
  61. Wang L, Dai W, Lu L. Stress-induced c-Jun activation mediated by Polo-like kinase 3 in corneal epithelial cells. J Biol Chem. 2007;282:32121–32127
  62. Wang Q, Xie S, Chen J, Fukasawa K, Naik U, Traganos F, et al. Cell cycle arrest and apoptosis induced by human Polo-like kinase 3 is mediated through perturbation of microtubule integrity. Mol Cell Biol. 2002;22:3450–3459
  63. Li Z, Niu J, Uwagawa T, Peng B, Chiao PJ. Function of polo-like kinase 3 in NF-kappaB-mediated proapoptotic response. J Biol Chem. 2005;280:16843–16850
  64. Syed N, Smith P, Sullivan A, Spender LC, Dyer M, Karran L, et al. Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignancies. Blood. 2006;107:250–256
  65. Mancini M, Machamer CE, Roy S, Nicholson DW, Thornberry NA, Casciola-Rosen LA, et al. Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis. J Cell Biol. 2000;149(3):603–612
  66. Chiu R, Novikov L, Mukherjee S, Shields D. A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis. J Cell Biol. 2002;159(4):637–648
  67. Lane JD, Lucocq J, Pryde J, Barr FA, Woodman PG, Allan VJ, et al. Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis. J Cell Biol. 2002;156(3):495–509
  68. Tinel A, Tschopp J, The PIDDosome . a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science. 2004;304(5672):843–846
  69. Maag RS, Mancini M, Rosen A, Machamer CE. Caspase-resistant Golgin-160 disrupts apoptosis induced by secretory pathway stress and ligation of death receptors. Mol Biol Cell. 2005;16(6):3019–3027
  70. Hauser HP, Bardroff M, Pyrowolakis G, Jentsch S. A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors. J Cell Biol. 1998;141(6):1415–1422
  71. Malisan F, Testi R. GD3 ganglioside and apoptosis. Biochim Biophys Acta. 2002;1585(2-3):179–187
  72. Rippo MR, Malisan F, Ravagnan L, Tomassini B, Condo I, Costantini P, et al. GD3 ganglioside directly targets mitochondria in a bcl-2-controlled fashion. FASEB J. 2000;14(13):2047–2054
  73. Tomassini B, Malisan F, Franchi L, Nicolo C, Calvo GB, Saito T, et al. Calnexin suppresses GD3 synthase-induced apoptosis. FASEB J. 2004;18(13):1553–1555
  74. Cristea IM, Degli Esposti M. Membrane lipids and cell death: an overview. Chem Phys Lipids. 2004;129(2):133–160
  75. Bennett M, Macdonald K, Chan SW, Luzio JP, Simari R, Weissberg P. Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science. 1998;282(5387):290–293
  76. Arvan P, Zhao X, Ramos-Castaneda J, Chang A. Secretory pathway quality control operating in Golgi, plasmalemmal, and endosomal systems. Traffic. 2002;3(11):771–780
  77. Linder S, Shoshan MC. Lysosomes and endoplasmic reticulum: targets for improved, selective anticancer therapy. Drug Resist Updat. 2005;8(4):199–204
  78. Carew JS, Nawrocki ST, Krupnik YV, Dunner K, McConkey DJ, Keating MJ, et al. Targeting endoplasmic reticulum protein transport: a novel strategy to kill malignant B cells and overcome fludarabine resistance in CLL. Blood. 2006;107(1):222–231
  79. Jaattela M. Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene. 2004;23(16):2746–2756
  80. Carew JS, Nawrocki ST, Xu RH, Dunner K, McConkey DJ, Wierda WG, et al. Increased mitochondrial biogenesis in primary leukemia cells: the role of endogenous nitric oxide and impact on sensitivity to fludarabine. Leukemia. 2004;18(12):1934–1940
  81. Donaldson JG, Cassel D, Kahn RA, Klausner RD. ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein beta-COP to Golgi membranes. Proc Natl Acad Sci USA. 1992;89(14):6408–6412
  82. Cheung HH, Lynn Kelly N, Liston P, Korneluk RG. Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: a role for the IAPs. Exp Cell Res. 2006;312(12):2347–2357
  83. Shao RG, Shimizu T, Pommier Y. Brefeldin A is a potent inducer of apoptosis in human cancer cells independently of p53. Exp Cell Res. 1996;227(2):190–196
  84. Wallen E, Sellers RG, Peehl DM. Brefeldin A induces p53-independent apoptosis in primary cultures of human prostatic cancer cells. Urol. 2000;164:836–841
  85. Salles FT, Hespanhol AM, Jaeger RG, Marques MM. Brefeldin-A induces apoptosis in human adenoid cystic carcinoma cultured cells. Oral Oncol. 2004;40(6):585–590
  86. Boya P, Cohen I, Zamzami N, Vieira HL, Kroemer G. Endoplasmic reticulum stress-induced cell death requires mitochondrial membrane permeabilization. Cell Death Differ. 2002;9(4):465–467
  87. Wlodkowic D, Skommer J, Pelkonen J. Brefeldin A triggers apoptosis associated with mitochondrial breach and enhances HA14-1- and anti-Fas-mediated cell killing in follicular lymphoma cells. Leukemia Res. 2007;31(12):1687–1700
  88. Sausville EA, Duncan KL, Senderowicz A, Plowman J, Randazzo PA, Kahn R, et al. antiproliferative effect in vitro and antitumor activity in vivo of brefeldin A. Cancer J Sci Am. 1996;2(1):52–58
  89. Phillips LR, Supko JG, Malspeis L. Analysis of Brefeldin A in plasma by gas chromatography with electron capture. Anal Biochem. 1993;211:16–22
  90. Phillips LR, Wolfe TL, Malspeis L, Supko JG. Analysis of brefeldin A and the prodrug breflate in plasma by gas chromatography with mass selective detection. J Pharm Biomed Anal. 1998;16(8):1301–1309
  91. Brown JM, Attardi LD. The role of apoptosis in cancer development and treatment response. Nat Rev Cancer. 2005;5(3):231–237
  92. Green DR, Kroemer G. Pharmacological manipulation of cell death: clinical applications in sight?. J Clin Invest. 2005;115(10):2610–2617
  93. Chapman JR, Tazaki H, Mallouh C, Konno S. Mechanism of Brefeldin A-induced growth inhibition and cell death in human prostatic carcinoma cells. Mol Urol. 1999;3(1):11–16
  94. Tinhoffer I, Anether G, Senfter M, Pfaller K, Bernhard D, Hara M, et al. Stressful death of T-ALL tumor cells after treatment with the anti-tumor agent Tetrocarcin-A. FASEB J. 2002;16:1295–1297
  95. Anether G, Tinhoffer I, Greil R. Tetrocarcin-A-induced ER stress mediates apoptosis in B-CLL cells via a Bcl-2-independent pathway. Blood. 2003;101(11):4561–4567
  96. Denmeade SR, Isaacs JT. The SERCA pump as a therapeutic target: making a “smart bomb” for prostate cancer. Cancer Biol & Ther. 2005;4(1):14–22
  97. Nawrocki ST, Carew JS, Pino MS, Highshaw RA, Dunner K, Huang P, et al. Bortezomib sensitizes pancreatic cancer cells to endoplasmic reticulum stress-mediated apoptosis. Cancer Res. 2005;65(24):11658–11666
  98. Hoeller D, Dikic I. Targeting the ubiquitin system in cancer therapy. Nature. 2009;458(7237):438–444
  99. Bennett MK, Kirk CJ. Development of proteasome inhibitors in oncology and autoimmune diseases. Curr Opin Drug Discov Dev. 2008;11(5):616–625
  100. Burger AM, Seth AK. The ubiquitin-mediated protein degradation pathway in cancer: therapeutic implications. Eur J Cancer. 2004;40(15):2217–2229
  101. Hill DS, Martin S, Armstrong JL, Flockhart R, Tonison JJ, Simpson DG, et al. Combining the endoplasmic reticulum stress-inducing agents bortezomib and fenretinide as a novel therapeutic strategy for metastatic melanoma. Clin Cancer Res. 2009;15(4):1192–1198
  102. Wang Q, Mora-Jensen H, Weniger MA, Perez-Galan P, Wolford C, Hai T, et al. ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc Natl Acad Sci USA. 2009;106(7):2200–2205
  103. Boelens J, Lust S, Offner F, Bracke ME, Vanhoecke BW. The endoplasmic reticulum: a target for new anticancer drugs. In Vivo. 2007;21(2):215–226

PII: S0145-2126(09)00276-8

doi: 10.1016/j.leukres.2009.05.025

Leukemia Research
Volume 33, Issue 11 , Pages 1440-1447 , November 2009