Advertisement

Apoptosis

, Volume 15, Issue 10, pp 1211–1222 | Cite as

TRAIL-induced apoptosis of human melanoma cells involves activation of caspase-4

  • Zhi Gang Mao
  • Chen Chen Jiang
  • Fan Yang
  • Rick F. Thorne
  • Peter Hersey
  • Xu Dong Zhang
Original Paper

Abstract

Although it is conventionally regarded as an inflammatory caspase, recent studies have shown that caspase-4 plays a role in induction of apoptosis by endoplasmic reticulum (ER) stress. We report here that activation of caspase-4 is also involved in induction of apoptosis by TNF-related apoptosis-inducing ligand (TRAIL) in human melanoma cells. Treatment with TRAIL resulted in activation of caspase-4. This appeared to be mediated by caspase-3, in that caspase-4 was activated later than caspase-8, -9, and -3, and that inhibition of caspase-3 blocked TRAIL-induced caspase-4 activation. Notably, TRAIL triggered ER stress in melanoma cells as shown by up-regulation of the GRP78 protein and the spliced form of XBP-1 mRNA. This seemed to be necessary for activation of caspase-4, as activation of caspase-3 by agents that did not trigger ER stress did not cause activation of caspase-4. Importantly, inhibition of caspase-4 also partially blocked caspase-3 activation, suggesting that activation of caspase-4 may be positive feed-back mechanism to further enhance caspase-3 activation. Collectively, these results show that activation of caspase-4 contributes to TRAIL-induced apoptosis and is associated with induction of ER stress by TRAIL in melanoma cells, and may have important implications for improving therapeutic efficacies of TRAIL in melanoma.

Keywords

TRAIL Caspase-4 Melanoma Apoptosis 

Notes

Acknowledgments

This work was supported by the NSW State Cancer Council, the Melanoma and Skin Cancer Research Institute Sydney, the Hunter Melanoma Foundation, NSW, and the National Health and Medical Research Council, Australia. X. D. Zhang is a Cancer Institute NSW Fellow.

References

  1. 1.
    Griffith TS, Lynch DH (1998) TRAIL: a molecule with multiple receptors and control mechanisms. Curr Opin Immunol 10:559–563CrossRefPubMedGoogle Scholar
  2. 2.
    Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (1997) The receptor for the cytotoxic ligand TRAIL. Science 276:111–113CrossRefPubMedGoogle Scholar
  3. 3.
    Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J (1997) TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity 7:831–836CrossRefPubMedGoogle Scholar
  4. 4.
    Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A (2000) Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 12:611–620CrossRefPubMedGoogle Scholar
  5. 5.
    Yamada H, Tada-Oikawa S, Uchida A, Kawanishi S (1999) TRAIL causes cleavage of bid by caspase-8 and loss of mitochondrial membrane potential resulting in apoptosis in BJAB cells. Biochem Biophys Res Commun 265:130–133CrossRefPubMedGoogle Scholar
  6. 6.
    Han J, Goldstein LA, Gastman BR, Rabinowich H (2006) Interrelated roles for Mcl-1 and BIM in regulation of TRAIL-mediated mitochondrial apoptosis. J Biol Chem 281:10153–10163CrossRefPubMedGoogle Scholar
  7. 7.
    Gillespie S, Borrow J, Zhang XD, Hersey P (2006) Bim plays a crucial role in synergistic induction of apoptosis by the histone deacetylase inhibitor SBHA and TRAIL in melanoma cells. Apoptosis 11:2251–2265CrossRefPubMedGoogle Scholar
  8. 8.
    Wagner KW, Engels IH, Deveraux QL (2004) Caspase-2 can function upstream of bid cleavage in the TRAIL apoptosis pathway. J Biol Chem 279:35047–35052CrossRefPubMedGoogle Scholar
  9. 9.
    Shin S, Lee Y, Kim W, Ko H, Choi H, Kim K (2005) Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8. EMBO J 24:3532–3542CrossRefPubMedGoogle Scholar
  10. 10.
    Martinon F, Tschopp J (2007) Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ 14:10–22CrossRefPubMedGoogle Scholar
  11. 11.
    Kamada S, Funahashi Y, Tsujimoto Y (1997) Caspase-4 and caspase-5, members of the ICE/CED-3 family of cysteine proteases, are CrmA-inhibitable proteases. Cell Death Differ 4:473–478CrossRefPubMedGoogle Scholar
  12. 12.
    Kamada S, Washida M, Hasegawa J, Kusano H, Funahashi Y, Tsujimoto Y (1997) Involvement of caspase-4(-like) protease in Fas-mediated apoptotic pathway. Oncogene 15:285–290CrossRefPubMedGoogle Scholar
  13. 13.
    Hitomi J, Katayama T, Eguchi Y, Kudo T, Taniguchi M, Koyama Y, Manabe T, Yamagishi S, Bando Y, Imaizumi K, Tsujimoto Y, Tohyama M (2004) Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and a beta-induced cell death. J Cell Biol 165:347–356CrossRefPubMedGoogle Scholar
  14. 14.
    Fischer H, Koenig U, Eckhart L, Tschachler E (2002) Human caspase 12 has acquired deleterious mutations. Biochem Biophys Res Commun 293:722–726CrossRefPubMedGoogle Scholar
  15. 15.
    Boyce M, Yuan J (2006) Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ 13:363–373CrossRefPubMedGoogle Scholar
  16. 16.
    Jiang CC, Chen LH, Gillespie S, Wang YF, Kiejda KA, Zhang XD, Hersey P (2007) Inhibition of MEK sensitizes human melanoma cells to endoplasmic reticulum stress-induced apoptosis. Cancer Res 67:9750–9761CrossRefPubMedGoogle Scholar
  17. 17.
    Ferri KF, Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat Cell Biol 3:E255–E263CrossRefPubMedGoogle Scholar
  18. 18.
    Obeng EA, Boise LH (2005) Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis. J Biol Chem 280:29578–29587CrossRefPubMedGoogle Scholar
  19. 19.
    Saleh M, Mathison JC, Wolinski MK, Bensinger SJ, Fitzgerald P, Droin N, Ulevitch RJ, Green DR, Nicholson DW (2006) Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice. Nature 440:1064–1068CrossRefPubMedGoogle Scholar
  20. 20.
    Lee AS (2007) GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res 67:3496–3499CrossRefPubMedGoogle Scholar
  21. 21.
    Li J, Lee AS (2006) Stress induction of GRP78/BiP and its role in cancer. Curr Mol Med 6:45–54CrossRefPubMedGoogle Scholar
  22. 22.
    Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403:98–103CrossRefPubMedGoogle Scholar
  23. 23.
    Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M (2001) 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 276:35–40Google Scholar
  24. 24.
    Hersey P, Zhang XD (2001) How melanoma cells evade trail-induced apoptosis. Nat Rev Cancer 1:142–150CrossRefPubMedGoogle Scholar
  25. 25.
    Zhang XD, Zhang XY, Gray CP, Nguyen T, Hersey P (2001) Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of human melanoma is regulated by smac/DIABLO release from mitochondria. Cancer Res 61:7339–7348PubMedGoogle Scholar
  26. 26.
    Chen LH, Jiang CC, Watts R, Thorne RF, Kiejda KA, Zhang XD, Hersey P (2008) Inhibition of endoplasmic reticulum stress-induced apoptosis of melanoma cells by the ARC protein. Cancer Res 68:834–842CrossRefPubMedGoogle Scholar
  27. 27.
    Nakamura M, Gotoh T, Okuno Y, Tatetsu H, Sonoki T, Uneda S, Mori M, Mitsuya H, Hata H (2006) Activation of the endoplasmic reticulum stress pathway is associated with survival of myeloma cells. Leuk Lymphoma 47:531–539CrossRefPubMedGoogle Scholar
  28. 28.
    Wang YF, Jiang CC, Kiejda KA, Gillespie S, Zhang XD, Hersey P (2007) Apoptosis induction in human melanoma cells by inhibition of MEK is caspase-independent and mediated by the Bcl-2 family members PUMA, Bim, and Mcl-1. Clin Cancer Res 13:4934–4942CrossRefPubMedGoogle Scholar
  29. 29.
    Fu Y, Li J, Lee AS (2007) GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation-induced apoptosis. Cancer Res 67:3734–3740CrossRefPubMedGoogle Scholar
  30. 30.
    Zhang XD, Gillespie SK, Hersey P (2004) Staurosporine induces apoptosis of melanoma by both caspase-dependent and -independent apoptotic pathways. Mol Cancer Ther 3:187–197PubMedGoogle Scholar
  31. 31.
    Hirota M, Kitagaki M, Itagaki H, Aiba S (2006) Quantitative measurement of spliced XBP1 mRNA as an indicator of endoplasmic reticulum stress. J Toxicol Sci 31:149–156CrossRefPubMedGoogle Scholar
  32. 32.
    Lee AS (2005) The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 35:373–381CrossRefPubMedGoogle Scholar
  33. 33.
    Zhang XD, Wu JJ, Gillespie S, Borrow J, Hersey P (2006) Human melanoma cells selected for resistance to apoptosis by prolonged exposure to tumor necrosis factor-related apoptosis-inducing ligand are more vulnerable to necrotic cell death induced by cisplatin. Clin Cancer Res 12:1355–1364CrossRefPubMedGoogle Scholar
  34. 34.
    Zhu BK, Wang P, Zhang XD, Jiang CC, Chen LH, Avery-Kiejda KA, Watts R, Hersey P (2008) Activation of Jun N-terminal kinase is a mediator of vincristine-induced apoptosis of melanoma cells. Anticancer Drugs 19:189–200CrossRefPubMedGoogle Scholar
  35. 35.
    Yang X, Wang J, Liu C, Grizzle WE, Yu S, Zhang S, Barnes S, Koopman WJ, Mountz JD, Kimberly RP, Zhang HG (2005) Cleavage of p53-vimentin complex enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of rheumatoid arthritis synovial fibroblasts. Am J Pathol 167:705–719PubMedGoogle Scholar
  36. 36.
    Burikhanov R, Zhao Y, Goswami A, Qiu S, Schwarze SR, Rangnekar VM (2009) The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis. Cell 138:377–388CrossRefPubMedGoogle Scholar
  37. 37.
    Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ (1999) Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol 144:281–292CrossRefPubMedGoogle Scholar
  38. 38.
    Chen LH, Jiang CC, Kiejda KA, Wang YF, Thorne RF, Zhang XD, Hersey P (2007) Thapsigargin sensitizes human melanoma cells to TRAIL-induced apoptosis by up-regulation of TRAIL-R2 through the unfolded protein response. Carcinogenesis 28:2328–2336CrossRefPubMedGoogle Scholar
  39. 39.
    Jiang CC, Chen LH, Gillespie S, Kiejda KA, Mhaidat N, Wang YF, Thorne R, Zhang XD, Hersey P (2007) Tunicamycin sensitizes human melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by up-regulation of TRAIL-R2 via the unfolded protein response. Cancer Res 67:5880–5888CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Immunology and Oncology UnitNewcastle Misericordiae HospitalNewcastleAustralia

Personalised recommendations