Skip to main content
SpringerLink
Log in

Apoptotic Caspases in Promoting Cancer: Implications from Their Roles in Development and Tissue Homeostasis

  • Chapter
  • First Online:
Apoptosis in Cancer Pathogenesis and Anti-cancer Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 930))

Abstract

Apoptosis, a major form of programmed cell death, is an important mechanism to remove extra or unwanted cells during development. In tissue homeostasis apoptosis also acts as a monitoring machinery to eliminate damaged cells in response to environmental stresses. During these processes, caspases, a group of proteases, have been well defined as key drivers of cell death. However, a wealth of evidence is emerging which supports the existence of many other non-apoptotic functions of these caspases, which are essential not only in proper organism development but also in tissue homeostasis and post-injury recovery. In particular, apoptotic caspases in stress-induced dying cells can activate mitogenic signals leading to proliferation of neighbouring cells, a phenomenon termed apoptosis-induced proliferation. Apparently, such non-apoptotic functions of caspases need to be controlled and restrained in a context-dependent manner during development to prevent their detrimental effects. Intriguingly, accumulating studies suggest that cancer cells are able to utilise these functions of caspases to their advantage to enable their survival, proliferation and metastasis in order to grow and progress. This book chapter will review non-apoptotic functions of the caspases in development and tissue homeostasis with focus on how these cellular processes can be hijacked by cancer cells and contribute to tumourigenesis.

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Jacobson MD, Weil M, Raff MC. Programmed cell death in animal development. Cell. 1997;88:347–54.

    Article  CAS  PubMed  Google Scholar 

  2. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ellis HM, Horvitz HR. Genetic control of programmed cell death in the nematode C. elegans. Cell. 1986;44:817–29.

    Article  CAS  PubMed  Google Scholar 

  4. Ellis RE, Yuan JY, Horvitz HR. Mechanisms and functions of cell death. Annu Rev Cell Biol. 1991;7:663–98.

    Article  CAS  PubMed  Google Scholar 

  5. Miura M. Active participation of cell death in development and organismal homeostasis. Dev Growth Differ. 2011;53:125–36.

    Article  CAS  PubMed  Google Scholar 

  6. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995;267:1456–62.

    Article  CAS  PubMed  Google Scholar 

  7. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  CAS  PubMed  Google Scholar 

  8. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  9. Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770–6.

    Article  CAS  PubMed  Google Scholar 

  10. Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998;281:1312–6.

    Article  CAS  PubMed  Google Scholar 

  11. Connolly PF, Jager R, Fearnhead HO. New roles for old enzymes: killer caspases as the engine of cell behavior changes. Front Physiol. 2014;5:149.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kuranaga E. Caspase signaling in animal development. Dev Growth Differ. 2011;53:137–48.

    Article  CAS  PubMed  Google Scholar 

  13. Miura M. Apoptotic and nonapoptotic caspase functions in animal development. Cold Spring Harb Perspect Biol. 2012;4:a008664.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Shalini S, Dorstyn L, Dawar S, Kumar S. Old, new and emerging functions of caspases. Cell Death Differ. 2015;22:526–39.

    Article  CAS  PubMed  Google Scholar 

  15. Degterev A, Yuan J. Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol. 2008;9:378–90.

    Article  CAS  PubMed  Google Scholar 

  16. Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell. 2011;147:742–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Green DR, Galluzzi L, Kroemer G. Cell biology. Metabolic control of cell death. Science. 2014;345:1250256.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Yamaguchi Y, Miura M. Programmed cell death in neurodevelopment. Dev Cell. 2015;32:478–90.

    Article  CAS  PubMed  Google Scholar 

  19. Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem. 1999;68:383–424.

    Article  CAS  PubMed  Google Scholar 

  20. Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell. 2014;157:1013–22.

    Article  CAS  PubMed  Google Scholar 

  21. Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, Vandenabeele P. Caspases in cell survival, proliferation and differentiation. Cell Death Differ. 2007;14:44–55.

    Article  CAS  PubMed  Google Scholar 

  22. Vanaja SK, Rathinam VA, Fitzgerald KA. Mechanisms of inflammasome activation: recent advances and novel insights. Trends Cell Biol. 2015;25:308–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Eckhart L, Ballaun C, Hermann M, Vandeberg JL, Sipos W, Uthman A, Fischer H, Tschachler E. Identification of novel mammalian caspases reveals an important role of gene loss in shaping the human caspase repertoire. Mol Biol Evol. 2008;25:831–41.

    Article  CAS  PubMed  Google Scholar 

  24. Degterev A, Boyce M, Yuan J. A decade of caspases. Oncogene. 2003;22:8543–67.

    Article  CAS  PubMed  Google Scholar 

  25. Chowdhury I, Tharakan B, Bhat GK. Caspases—an update. Comp Biochem Physiol B Biochem Mol Biol. 2008;151:10–27.

    Article  PubMed  CAS  Google Scholar 

  26. Kumar S. Caspase function in programmed cell death. Cell Death Differ. 2007;14:32–43.

    Article  CAS  PubMed  Google Scholar 

  27. Yan N, Shi Y. Mechanisms of apoptosis through structural biology. Annu Rev Cell Dev Biol. 2005;21:35–56.

    Article  CAS  PubMed  Google Scholar 

  28. Lettre G, Hengartner MO. Developmental apoptosis in C. elegans: a complex CEDnario. Nat Rev Mol Cell Biol. 2006;7:97–108.

    Article  CAS  PubMed  Google Scholar 

  29. Conradt B, Xue D. Programmed cell death. WormBook; 2005. p. 1–13.

    Google Scholar 

  30. Kornbluth S, White K. Apoptosis in Drosophila: neither fish nor fowl (nor man, nor worm). J Cell Sci. 2005;118:1779–87.

    Article  CAS  PubMed  Google Scholar 

  31. Steller H. Regulation of apoptosis in Drosophila. Cell Death Differ. 2008;15:1132–8.

    Article  CAS  PubMed  Google Scholar 

  32. Goyal L, McCall K, Agapite J, Hartwieg E, Steller H. Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function. EMBO J. 2000;19:589–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lisi S, Mazzon I, White K. Diverse domains of THREAD/DIAP1 are required to inhibit apoptosis induced by REAPER and HID in Drosophila. Genetics. 2000;154:669–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang SL, Hawkins CJ, Yoo SJ, Muller HA, Hay BA. The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. Cell. 1999;98:453–63.

    Article  CAS  PubMed  Google Scholar 

  35. Meier P, Silke J, Leevers SJ, Evan GI. The Drosophila caspase DRONC is regulated by DIAP1. EMBO J. 2000;19:598–611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wilson R, Goyal L, Ditzel M, Zachariou A, Baker DA, Agapite J, Steller H, Meier P. The DIAP1 RING finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis. Nat Cell Biol. 2002;4:445–50.

    Article  CAS  PubMed  Google Scholar 

  37. Hawkins CJ, Wang SL, Hay BA. A cloning method to identify caspases and their regulators in yeast: identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP-1. Proc Natl Acad Sci U S A. 1999;96:2885–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yan N, Wu JW, Chai J, Li W, Shi Y. Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim. Nat Struct Mol Biol. 2004;11:420–8.

    Article  CAS  PubMed  Google Scholar 

  39. Lee TV, Fan Y, Wang S, Srivastava M, Broemer M, Meier P, Bergmann A. Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation. PLoS Genet. 2011;7, e1002261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ryoo HD, Bergmann A, Gonen H, Ciechanover A, Steller H. Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1. Nat Cell Biol. 2002;4:432–8.

    Article  CAS  PubMed  Google Scholar 

  41. Yoo SJ, Huh JR, Muro I, Yu H, Wang L, Wang SL, Feldman RM, Clem RJ, Muller HA, Hay BA. Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms. Nat Cell Biol. 2002;4:416–24.

    Article  CAS  PubMed  Google Scholar 

  42. Chai J, Shi Y. Apoptosome and inflammasome: conserved machineries for caspase activation. Natl Sci Rev. 2014;1:101–18.

    Article  Google Scholar 

  43. Pang Y, Bai XC, Yan C, Hao Q, Chen Z, Wang JW, Scheres SH, Shi Y. Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila. Genes Dev. 2015;29:277–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Dorstyn L, Kumar S. A biochemical analysis of the activation of the Drosophila caspase DRONC. Cell Death Differ. 2008;15:461–70.

    Article  CAS  PubMed  Google Scholar 

  45. Hawkins CJ, Yoo SJ, Peterson EP, Wang SL, Vernooy SY, Hay BA. The Drosophila caspase DRONC cleaves following glutamate or aspartate and is regulated by DIAP1, HID, and GRIM. J Biol Chem. 2000;275:27084–93.

    CAS  PubMed  Google Scholar 

  46. Snipas SJ, Drag M, Stennicke HR, Salvesen GS. Activation mechanism and substrate specificity of the Drosophila initiator caspase DRONC. Cell Death Differ. 2008;15:938–45.

    Article  CAS  PubMed  Google Scholar 

  47. Abdelwahid E, Yokokura T, Krieser RJ, Balasundaram S, Fowle WH, White K. Mitochondrial disruption in Drosophila apoptosis. Dev Cell. 2007;12:793–806.

    Article  CAS  PubMed  Google Scholar 

  48. Claveria C, Albar JP, Serrano A, Buesa JM, Barbero JL, Martinez AC, Torres M. Drosophila grim induces apoptosis in mammalian cells. EMBO J. 1998;17:7199–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Claveria C, Caminero E, Martinez AC, Campuzano S, Torres M. GH3, a novel proapoptotic domain in Drosophila Grim, promotes a mitochondrial death pathway. EMBO J. 2002;21:3327–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Freel CD, Richardson DA, Thomenius MJ, Gan EC, Horn SR, Olson MR, Kornbluth S. Mitochondrial localization of Reaper to promote inhibitors of apoptosis protein degradation conferred by GH3 domain-lipid interactions. J Biol Chem. 2008;283:367–79.

    Article  CAS  PubMed  Google Scholar 

  51. Haining WN, Carboy-Newcomb C, Wei CL, Steller H. The proapoptotic function of Drosophila Hid is conserved in mammalian cells. Proc Natl Acad Sci U S A. 1999;96:4936–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Morishita J, Kang MJ, Fidelin K, Ryoo HD. CDK7 regulates the mitochondrial localization of a tail-anchored proapoptotic protein, Hid. Cell Rep. 2013;5:1481–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Olson MR, Holley CL, Gan EC, Colon-Ramos DA, Kaplan B, Kornbluth S. A GH3-like domain in reaper is required for mitochondrial localization and induction of IAP degradation. J Biol Chem. 2003;278:44758–68.

    Article  CAS  PubMed  Google Scholar 

  54. Thomenius M, Freel CD, Horn S, Krieser R, Abdelwahid E, Cannon R, Balasundaram S, White K, Kornbluth S. Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death. Cell Death Differ. 2011;18:1640–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Brachmann CB, Jassim OW, Wachsmuth BD, Cagan RL. The Drosophila bcl-2 family member dBorg-1 functions in the apoptotic response to UV-irradiation. Curr Biol. 2000;10:547–50.

    Article  CAS  PubMed  Google Scholar 

  56. Colussi PA, Quinn LM, Huang DC, Coombe M, Read SH, Richardson H, Kumar S. Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery. J Cell Biol. 2000;148:703–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Igaki T, Kanuka H, Inohara N, Sawamoto K, Nunez G, Okano H, Miura M. Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death. Proc Natl Acad Sci U S A. 2000;97:662–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Quinn L, Coombe M, Mills K, Daish T, Colussi P, Kumar S, Richardson H. Buffy, a Drosophila Bcl-2 protein, has anti-apoptotic and cell cycle inhibitory functions. EMBO J. 2003;22:3568–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhang H, Huang Q, Ke N, Matsuyama S, Hammock B, Godzik A, Reed JC. Drosophila pro-apoptotic Bcl-2/Bax homologue reveals evolutionary conservation of cell death mechanisms. J Biol Chem. 2000;275:27303–6.

    CAS  PubMed  Google Scholar 

  60. Doumanis J, Dorstyn L, Kumar S. Molecular determinants of the subcellular localization of the Drosophila Bcl-2 homologues DEBCL and BUFFY. Cell Death Differ. 2007;14:907–15.

    CAS  PubMed  Google Scholar 

  61. Gabriel B, Sureau F, Casselyn M, Teissie J, Petit PX. Retroactive pathway involving mitochondria in electroloaded cytochrome c-induced apoptosis. Protective properties of Bcl-2 and Bcl-XL. Exp Cell Res. 2003;289:195–210.

    Article  CAS  PubMed  Google Scholar 

  62. Vander Heiden MG, Chandel NS, Williamson EK, Schumacker PT, Thompson CB. Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell. 1997;91:627–37.

    Article  CAS  PubMed  Google Scholar 

  63. Xiong S, Mu T, Wang G, Jiang X. Mitochondria-mediated apoptosis in mammals. Protein Cell. 2014;5:737–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997;275:1129–32.

    Article  CAS  PubMed  Google Scholar 

  65. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES. Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. Mol Cell. 1998;1:949–57.

    Article  CAS  PubMed  Google Scholar 

  66. Kumar S, Colussi PA. Prodomains—adaptors—oligomerization: the pursuit of caspase activation in apoptosis. Trends Biochem Sci. 1999;24:1–4.

    Article  CAS  PubMed  Google Scholar 

  67. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305:626–9.

    Article  CAS  PubMed  Google Scholar 

  68. Silke J, Verhagen AM, Ekert PG, Vaux DL. Sequence as well as functional similarity for DIABLO/Smac and Grim, Reaper and Hid? Cell Death Differ. 2000;7:1275.

    Article  CAS  PubMed  Google Scholar 

  69. Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell. 2001;8:613–21.

    Article  CAS  PubMed  Google Scholar 

  70. Gottfried Y, Rotem A, Lotan R, Steller H, Larisch S. The mitochondrial ARTS protein promotes apoptosis through targeting XIAP. EMBO J. 2004;23:1627–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Larisch S, Yi Y, Lotan R, Kerner H, Eimerl S, Tony Parks W, Gottfried Y, Birkey Reffey S, De Caestecker MP, Danielpour D, Book-Melamed N, Timberg R, Duckett CS, Lechleider RJ, Steller H, Orly J, Kim SJ, Roberts AB. A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat Cell Biol. 2000;2:915–21.

    Article  CAS  PubMed  Google Scholar 

  72. Edison N, Zuri D, Maniv I, Bornstein B, Lev T, Gottfried Y, Kemeny S, Garcia-Fernandez M, Kagan J, Larisch S. The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and SMAC/Diablo. Cell Death Differ. 2012;19:356–68.

    Article  CAS  PubMed  Google Scholar 

  73. Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281:1305–8.

    Article  CAS  PubMed  Google Scholar 

  74. Lavrik I, Golks A, Krammer PH. Death receptor signaling. J Cell Sci. 2005;118:265–7.

    Article  CAS  PubMed  Google Scholar 

  75. Peter ME, Krammer PH. Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis. Curr Opin Immunol. 1998;10:545–51.

    Article  CAS  PubMed  Google Scholar 

  76. Juo P, Kuo CJ, Yuan J, Blenis J. Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Curr Biol. 1998;8:1001–8.

    Article  CAS  PubMed  Google Scholar 

  77. Medema JP, Scaffidi C, Kischkel FC, Shevchenko A, Mann M, Krammer PH, Peter ME. FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J. 1997;16:2794–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL, Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P, Wallach D. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity. 1998;9:267–76.

    Article  CAS  PubMed  Google Scholar 

  79. Chang DW, Xing Z, Capacio VL, Peter ME, Yang X. Interdimer processing mechanism of procaspase-8 activation. EMBO J. 2003;22:4132–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Guicciardi ME, Gores GJ. Life and death by death receptors. FASEB J. 2009;23:1625–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Igaki T, Kanda H, Yamamoto-Goto Y, Kanuka H, Kuranaga E, Aigaki T, Miura M. Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J. 2002;21:3009–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Moreno E, Yan M, Basler K. Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily. Curr Biol. 2002;12:1263–8.

    Article  CAS  PubMed  Google Scholar 

  83. Andersen DS, Colombani J, Palmerini V, Chakrabandhu K, Boone E, Rothlisberger M, Toggweiler J, Basler K, Mapelli M, Hueber AO, Leopold P. The Drosophila TNF receptor Grindelwald couples loss of cell polarity and neoplastic growth. Nature. 2015;522:482–6.

    Article  CAS  PubMed  Google Scholar 

  84. Kanda H, Igaki T, Kanuka H, Yagi T, Miura M. Wengen, a member of the Drosophila tumor necrosis factor receptor superfamily, is required for Eiger signaling. J Biol Chem. 2002;277:28372–5.

    Article  CAS  PubMed  Google Scholar 

  85. Kanda H, Igaki T, Okano H, Miura M. Conserved metabolic energy production pathways govern Eiger/TNF-induced nonapoptotic cell death. Proc Natl Acad Sci U S A. 2011;108:18977–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ma X, Huang J, Yang L, Yang Y, Li W, Xue L. NOPO modulates Egr-induced JNK-independent cell death in Drosophila. Cell Res. 2012;22:425–31.

    Article  CAS  PubMed  Google Scholar 

  87. Shlevkov E, Morata G. A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila. Cell Death Differ. 2012;19:451–60.

    Article  CAS  PubMed  Google Scholar 

  88. Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB. Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis. 2002;23:143–50.

    Article  CAS  PubMed  Google Scholar 

  89. Kantari C, Walczak H. Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta. 2011;1813:558–63.

    Article  CAS  PubMed  Google Scholar 

  90. Tang D, Lahti JM, Kidd VJ. Caspase-8 activation and bid cleavage contribute to MCF7 cellular execution in a caspase-3-dependent manner during staurosporine-mediated apoptosis. J Biol Chem. 2000;275:9303–7.

    Article  CAS  PubMed  Google Scholar 

  91. Nonomura K, Yamaguchi Y, Hamachi M, Koike M, Uchiyama Y, Nakazato K, Mochizuki A, Sakaue-Sawano A, Miyawaki A, Yoshida H, Kuida K, Miura M. Local apoptosis modulates early mammalian brain development through the elimination of morphogen-producing cells. Dev Cell. 2013;27:621–34.

    Article  CAS  PubMed  Google Scholar 

  92. Monier B, Gettings M, Gay G, Mangeat T, Schott S, Guarner A, Suzanne M. Apico-basal forces exerted by apoptotic cells drive epithelium folding. Nature. 2015;518:245–8.

    Article  CAS  PubMed  Google Scholar 

  93. Kuipers D, Mehonic A, Kajita M, Peter L, Fujita Y, Duke T, Charras G, Gale JE. Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours. J Cell Sci. 2014;127:1229–41.

    Article  CAS  PubMed  Google Scholar 

  94. Kang Y, Bashirullah A. A steroid-controlled global switch in sensitivity to apoptosis during Drosophila development. Dev Biol. 2014;386:34–41.

    Article  CAS  PubMed  Google Scholar 

  95. Fan Y, Bergmann A. Multiple mechanisms modulate distinct cellular susceptibilities toward apoptosis in the developing Drosophila eye. Dev Cell. 2014;30:48–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Hilgers V, Bushati N, Cohen SM. Drosophila microRNAs 263a/b confer robustness during development by protecting nascent sense organs from apoptosis. PLoS Biol. 2010;8, e1000396.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Pernaute B, Spruce T, Smith KM, Sanchez-Nieto JM, Manzanares M, Cobb B, Rodriguez TA. MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM. Genes Dev. 2014;28:1873–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kuranaga E. Beyond apoptosis: caspase regulatory mechanisms and functions in vivo. Genes Cells. 2012;17:83–97.

    Article  CAS  PubMed  Google Scholar 

  99. Kuranaga E, Miura M. Nonapoptotic functions of caspases: caspases as regulatory molecules for immunity and cell-fate determination. Trends Cell Biol. 2007;17:135–44.

    Article  CAS  PubMed  Google Scholar 

  100. Haynie J, Bryant P. The effects of X-rays on the proliferation dynamics of cells in the imaginal wing disc of Drosophila melanogaster. Wilhelm Rouxs Arch Dev Biol. 1977;183:85–100.

    Article  Google Scholar 

  101. Li F, Huang Q, Chen J, Peng Y, Roop DR, Bedford JS, Li CY. Apoptotic cells activate the “phoenix rising” pathway to promote wound healing and tissue regeneration. Sci Signal. 2010;3:ra13.

    PubMed  PubMed Central  Google Scholar 

  102. Chera S, Ghila L, Dobretz K, Wenger Y, Bauer C, Buzgariu W, Martinou JC, Galliot B. Apoptotic cells provide an unexpected source of Wnt3 signaling to drive hydra head regeneration. Dev Cell. 2009;17:279–89.

    Article  CAS  PubMed  Google Scholar 

  103. Fan Y, Bergmann A. Distinct mechanisms of apoptosis-induced compensatory proliferation in proliferating and differentiating tissues in the Drosophila eye. Dev Cell. 2008;14:399–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Huh JR, Guo M, Hay BA. Compensatory proliferation induced by cell death in the Drosophila wing disc requires activity of the apical cell death caspase Dronc in a nonapoptotic role. Curr Biol. 2004;14:1262–6.

    Article  CAS  PubMed  Google Scholar 

  105. Kondo S, Senoo-Matsuda N, Hiromi Y, Miura M. DRONC coordinates cell death and compensatory proliferation. Mol Cell Biol. 2006;26:7258–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Bergmann A, Steller H. Apoptosis, stem cells, and tissue regeneration. Sci Signal. 2010;3:re8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Fan Y, Bergmann A. Apoptosis-induced compensatory proliferation. The cell is dead. Long live the cell! Trends Cell Biol. 2008;18:467–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Mollereau B, Perez-Garijo A, Bergmann A, Miura M, Gerlitz O, Ryoo HD, Steller H, Morata G. Compensatory proliferation and apoptosis-induced proliferation: a need for clarification. Cell Death Differ. 2013;20:181.

    Article  CAS  PubMed  Google Scholar 

  109. Ryoo HD, Bergmann A. The role of apoptosis-induced proliferation for regeneration and cancer. Cold Spring Harb Perspect Biol. 2012;4:a008797.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Fan Y, Wang S, Hernandez J, Yenigun VB, Hertlein G, Fogarty CE, Lindblad JL, Bergmann A. Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila. PLoS Genet. 2014;10, e1004131.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Perez-Garijo A, Martin FA, Morata G. Caspase inhibition during apoptosis causes abnormal signalling and developmental aberrations in Drosophila. Development. 2004;131:5591–8.

    Article  CAS  PubMed  Google Scholar 

  112. Ryoo HD, Gorenc T, Steller H. Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways. Dev Cell. 2004;7:491–501.

    Article  CAS  PubMed  Google Scholar 

  113. Wells BS, Yoshida E, Johnston LA. Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity. Curr Biol. 2006;16:1606–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Hay BA, Wolff T, Rubin GM. Expression of baculovirus P35 prevents cell death in Drosophila. Development. 1994;120:2121–9.

    CAS  PubMed  Google Scholar 

  115. Perez-Garijo A, Shlevkov E, Morata G. The role of Dpp and Wg in compensatory proliferation and in the formation of hyperplastic overgrowths caused by apoptotic cells in the Drosophila wing disc. Development. 2009;136:1169–77.

    Article  CAS  PubMed  Google Scholar 

  116. Bergantinos C, Corominas M, Serras F. Cell death-induced regeneration in wing imaginal discs requires JNK signalling. Development. 2010;137:1169–79.

    Article  CAS  PubMed  Google Scholar 

  117. Martin FA, Perez-Garijo A, Morata G. Apoptosis in Drosophila: compensatory proliferation and undead cells. Int J Dev Biol. 2009;53:1341–7.

    Article  PubMed  Google Scholar 

  118. Smith-Bolton RK, Worley MI, Kanda H, Hariharan IK. Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc. Dev Cell. 2009;16:797–809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Sun G, Irvine KD. Regulation of Hippo signaling by Jun kinase signaling during compensatory cell proliferation and regeneration, and in neoplastic tumors. Dev Biol. 2011;350:139–51.

    Article  CAS  PubMed  Google Scholar 

  120. Sun G, Irvine KD. Ajuba family proteins link JNK to Hippo signaling. Sci Signal. 2013;6:81.

    Article  CAS  Google Scholar 

  121. Tseng AS, Adams DS, Qiu D, Koustubhan P, Levin M. Apoptosis is required during early stages of tail regeneration in Xenopus laevis. Dev Biol. 2007;301:62–9.

    Article  CAS  PubMed  Google Scholar 

  122. Pellettieri J, Fitzgerald P, Watanabe S, Mancuso J, Green DR, Sanchez Alvarado A. Cell death and tissue remodeling in planarian regeneration. Dev Biol. 2010;338:76–85.

    Article  CAS  PubMed  Google Scholar 

  123. Pellettieri J, Sanchez Alvarado A. Cell turnover and adult tissue homeostasis: from humans to planarians. Annu Rev Genet. 2007;41:83–105.

    Article  CAS  PubMed  Google Scholar 

  124. Vlaskalin T, Wong CJ, Tsilfidis C. Growth and apoptosis during larval forelimb development and adult forelimb regeneration in the newt (Notophthalmus viridescens). Dev Genes Evol. 2004;214:423–31.

    Article  PubMed  Google Scholar 

  125. Jung Y, Witek RP, Syn WK, Choi SS, Omenetti A, Premont R, Guy CD, Diehl AM. Signals from dying hepatocytes trigger growth of liver progenitors. Gut. 2010;59:655–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 2009;136:1136–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005;310:1504–10.

    Article  CAS  PubMed  Google Scholar 

  128. Jager R, Fearnhead HO. “Dead cells talking”: the silent form of cell death is not so quiet. Biochem Res Int. 2012;2012:453838.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Moon RT, Kohn AD, de Ferrari GV, Kaykas A. WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet. 2004;5:691–701.

    Article  CAS  PubMed  Google Scholar 

  130. van Raam BJ, Salvesen GS. Proliferative versus apoptotic functions of caspase-8 Hetero or homo: the caspase-8 dimer controls cell fate. Biochim Biophys Acta. 2012;1824:113–22.

    Article  PubMed  CAS  Google Scholar 

  131. Beisner DR, Chen IL, Kolla RV, Hoffmann A, Hedrick SM. Cutting edge: innate immunity conferred by B cells is regulated by caspase-8. J Immunol. 2005;175:3469–73.

    Article  CAS  PubMed  Google Scholar 

  132. Salmena L, Lemmers B, Hakem A, Matysiak-Zablocki E, Murakami K, Au PY, Berry DM, Tamblyn L, Shehabeldin A, Migon E, Wakeham A, Bouchard D, Yeh WC, Mcglade JC, Ohashi PS, Hakem R. Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. Genes Dev. 2003;17:883–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Su H, Bidere N, Zheng L, Cubre A, Sakai K, Dale J, Salmena L, Hakem R, Straus S, Lenardo M. Requirement for caspase-8 in NF-kappaB activation by antigen receptor. Science. 2005;307:1465–8.

    Article  CAS  PubMed  Google Scholar 

  134. Oberst A, Green DR. It cuts both ways: reconciling the dual roles of caspase 8 in cell death and survival. Nat Rev Mol Cell Biol. 2011;12:757–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Zhou XD, Yu JP, Liu J, Luo HS, Chen HX, Yu HG. Overexpression of cellular FLICE-inhibitory protein (FLIP) in gastric adenocarcinoma. Clin Sci (Lond). 2004;106:397–405.

    Article  CAS  Google Scholar 

  136. Ghavami S, Hashemi M, Ande SR, Yeganeh B, Xiao W, Eshraghi M, Bus CJ, Kadkhoda K, Wiechec E, Halayko AJ, Los M. Apoptosis and cancer: mutations within caspase genes. J Med Genet. 2009;46:497–510.

    Article  CAS  PubMed  Google Scholar 

  137. Ili CG, Brebi P, Tapia O, Sandoval A, Lopez J, Garcia P, Leal P, Sidransky D, Guerrero-Preston R, Roa JC. Cellular FLICE-like inhibitory protein long form (c-FLIPL) overexpression is related to cervical cancer progression. Int J Gynecol Pathol. 2013;32:316–22.

    Article  CAS  PubMed  Google Scholar 

  138. Sharp DA, Lawrence DA, Ashkenazi A. Selective knockdown of the long variant of cellular FLICE inhibitory protein augments death receptor-mediated caspase-8 activation and apoptosis. J Biol Chem. 2005;280:19401–9.

    Article  CAS  PubMed  Google Scholar 

  139. Wang W, Wang S, Song X, Sima N, Xu X, Luo A, Chen G, Deng D, Xu Q, Meng L, Lu Y, Ma D. The relationship between c-FLIP expression and human papillomavirus E2 gene disruption in cervical carcinogenesis. Gynecol Oncol. 2007;105:571–7.

    Article  CAS  PubMed  Google Scholar 

  140. Hashimoto T, Kikkawa U, Kamada S. Contribution of caspase(s) to the cell cycle regulation at mitotic phase. PLoS One. 2011;6, e18449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Hashimoto T, Yamauchi L, Hunter T, Kikkawa U, Kamada S. Possible involvement of caspase-7 in cell cycle progression at mitosis. Genes Cells. 2008;13:609–21.

    Article  CAS  PubMed  Google Scholar 

  142. Eymin B, Sordet O, Droin N, Munsch B, Haugg M, van de Craen M, Vandenabeele P, Solary E. Caspase-induced proteolysis of the cyclin-dependent kinase inhibitor p27Kip1 mediates its anti-apoptotic activity. Oncogene. 1999;18:4839–47.

    Article  CAS  PubMed  Google Scholar 

  143. Khalil H, Peltzer N, Walicki J, Yang JY, Dubuis G, Gardiol N, Held W, Bigliardi P, Marsland B, Liaudet L, Widmann C. Caspase-3 protects stressed organs against cell death. Mol Cell Biol. 2012;32:4523–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Yang JY, Michod D, Walicki J, Murphy BM, Kasibhatla S, Martin SJ, Widmann C. Partial cleavage of RasGAP by caspases is required for cell survival in mild stress conditions. Mol Cell Biol. 2004;24:10425–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Yang JY, Widmann C. The RasGAP N-terminal fragment generated by caspase cleavage protects cells in a Ras/PI3K/Akt-dependent manner that does not rely on NFkappa B activation. J Biol Chem. 2002;277:14641–6.

    Article  CAS  PubMed  Google Scholar 

  146. Geiger TR, Peeper DS. Metastasis mechanisms. Biochim Biophys Acta. 2009;1796:293–308.

    CAS  PubMed  Google Scholar 

  147. Geisbrecht ER, Montell DJ. A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. Cell. 2004;118:111–25.

    Article  CAS  PubMed  Google Scholar 

  148. Kang TB, Ben-Moshe T, Varfolomeev EE, Pewzner-Jung Y, Yogev N, Jurewicz A, Waisman A, Brenner O, Haffner R, Gustafsson E, Ramakrishnan P, Lapidot T, Wallach D. Caspase-8 serves both apoptotic and nonapoptotic roles. J Immunol. 2004;173:2976–84.

    Article  CAS  PubMed  Google Scholar 

  149. Portela M, Richardson HE. Death takes a holiday—non-apoptotic role for caspases in cell migration and invasion. EMBO Rep. 2013;14:107–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Zhao X, Wang D, Zhao Z, Xiao Y, Sengupta S, Xiao Y, Zhang R, Lauber K, Wesselborg S, Feng L, Rose TM, Shen Y, Zhang J, Prestwich G, Xu Y. Caspase-3-dependent activation of calcium-independent phospholipase A2 enhances cell migration in non-apoptotic ovarian cancer cells. J Biol Chem. 2006;281:29357–68.

    Article  CAS  PubMed  Google Scholar 

  151. Brown M, Roulson JA, Hart CA, Tawadros T, Clarke NW. Arachidonic acid induction of Rho-mediated transendothelial migration in prostate cancer. Br J Cancer. 2014;110:2099–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Cheng YJ, Lee CH, Lin YP, Huang JY, Su CC, Chang WT, Yang BC. Caspase-3 enhances lung metastasis and cell migration in a protease-independent mechanism through the ERK pathway. Int J Cancer. 2008;123:1278–85.

    Article  CAS  PubMed  Google Scholar 

  153. Rudrapatna VA, Bangi E, Cagan RL. Caspase signalling in the absence of apoptosis drives Jnk-dependent invasion. EMBO Rep. 2013;14:172–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Na HJ, Hwang JY, Lee KS, Choi YK, Choe J, Kim JY, Moon HE, Kim KW, Koh GY, Lee H, Jeoung D, Won MH, Ha KS, Kwon YG, Kim YM. TRAIL negatively regulates VEGF-induced angiogenesis via caspase-8-mediated enzymatic and non-enzymatic functions. Angiogenesis. 2014;17:179–94.

    Article  CAS  PubMed  Google Scholar 

  155. Li F, He Z, Shen J, Huang Q, Li W, Liu X, He Y, Wolf F, Li CY. Apoptotic caspases regulate induction of iPSCs from human fibroblasts. Cell Stem Cell. 2010;7:508–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Chang DW, Xing Z, Pan Y, Algeciras-Schimnich A, Barnhart BC, Yaish-Ohad S, Peter ME, Yang X. c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J. 2002;21:3704–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Kim RJ, Nam JS. OCT4 expression enhances features of cancer stem cells in a mouse model of breast cancer. Lab Anim Res. 2011;27:147–52.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006;25:4798–811.

    Article  CAS  PubMed  Google Scholar 

  159. Dick JE. Stem cell concepts renew cancer research. Blood. 2008;112:4793–807.

    Article  CAS  PubMed  Google Scholar 

  160. Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, O’Sullivan B, He Z, Peng Y, Tan AC, Zhou L, Shen J, Han G, Wang XJ, Thorburn J, Thorburn A, Jimeno A, Raben D, Bedford JS, Li CY. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med. 2011;17:860–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Donato AL, Huang Q, Liu X, Li F, Zimmerman MA, Li CY. Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy. J Invest Dermatol. 2014;134:1686–92.

    Google Scholar 

  162. Nakopoulou L, Alexandrou P, Stefanaki K, Panayotopoulou E, Lazaris AC, Davaris PS. Immunohistochemical expression of caspase-3 as an adverse indicator of the clinical outcome in human breast cancer. Pathobiology. 2001;69:266–73.

    Article  CAS  PubMed  Google Scholar 

  163. Hu Q, Peng J, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Liu S, Wang H. Elevated cleaved caspase-3 is associated with shortened overall survival in several cancer types. Int J Clin Exp Pathol. 2014;7:5057–70.

    PubMed  PubMed Central  Google Scholar 

  164. Labi V, Erlacher M, Krumschnabel G, Manzl C, Tzankov A, Pinon J, Egle A, Villunger A. Apoptosis of leukocytes triggered by acute DNA damage promotes lymphoma formation. Genes Dev. 2010;24:1602–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Michalak EM, Vandenberg CJ, Delbridge AR, Wu L, Scott CL, Adams JM, Strasser A. Apoptosis-promoted tumorigenesis: gamma-irradiation-induced thymic lymphomagenesis requires Puma-driven leukocyte death. Genes Dev. 2010;24:1608–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011;475:222–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, Bast MA, Rosenwald A, Muller-Hermelink HK, Rimsza LM, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Jaffe ES, Lenz G, Connors JM, Staudt LM, Chan WC, Gascoyne RD. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010;362:875–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Willems JJ, Arnold BP, Gregory CD. Sinister self-sacrifice: the contribution of apoptosis to malignancy. Front Immunol. 2014;5:299.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  169. Ford CA, Petrova S, Pound JD, Voss JJ, Melville L, Paterson M, Farnworth SL, Gallimore AM, Cuff S, Wheadon H, Dobbin E, Ogden CA, Dumitriu IE, Dunbar DR, Murray PG, Ruckerl D, Allen JE, Hume DA, van Rooijen N, Goodlad JR, Freeman TC, Gregory CD. Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma. Curr Biol. 2015;25:577–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Lauber K, Bohn E, Krober SM, Xiao YJ, Blumenthal SG, Lindemann RK, Marini P, Wiedig C, Zobywalski A, Baksh S, Xu Y, Autenrieth IB, Schulze-Osthoff K, Belka C, Stuhler G, Wesselborg S. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell. 2003;113:717–30.

    Article  CAS  PubMed  Google Scholar 

  171. Ravichandran KS. Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. Immunity. 2011;35:445–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We apologise to our colleagues for omitting many relevant publications owing to space limitations. This work was supported by Marie Curie Career Integration Grant (CIG) 630846 from the European Union’s Seventh Framework Programme (FP7) and the Birmingham Fellowship, University of Birmingham, UK.

Author information

Authors and Affiliations

  1. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Catherine Dabrowska, Mingli Li & Yun Fan

Authors
  1. Catherine Dabrowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingli Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yun Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yun Fan .

Editor information

Editors and Affiliations

  1. MRC Centre for Inflammation Research, University of Edinburgh Queen’s Medical Research Institute, Edinburgh, United Kingdom

    Christopher D. Gregory

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Dabrowska, C., Li, M., Fan, Y. (2016). Apoptotic Caspases in Promoting Cancer: Implications from Their Roles in Development and Tissue Homeostasis. In: Gregory, C. (eds) Apoptosis in Cancer Pathogenesis and Anti-cancer Therapy. Advances in Experimental Medicine and Biology, vol 930. Springer, Cham. https://doi.org/10.1007/978-3-319-39406-0_4

Download citation

Publish with us

Policies and ethics

Search

Navigation