Abstract
Our previous studies revealed that Docetaxel-induced apoptosis of melanoma cells is entirely dependent on activation of the JNK signalling pathway. Here, we show that Docetaxel-induced apoptosis is mediated by induction of ER stress. This was shown by Docetaxel-induced activation of proteins involved in ER stress signalling namely GRP78, ATF6, IRE1α, and PERK/eIF2α. Knockdown of IRE1α by siRNA markedly inhibited Docetaxel-induced JNK activation and downstream targets of JNK indicating that activation of IRE1α was upstream of activation of the JNK. Co-immunoprecipitation experiments showed that activation of JNK is due to activation of ASK1 through formation of an IRE1α-TRAF2-ASK1 complex. ER stress mediated activation of the JNK pathway is downstream of activation of PKCδ in that downregulation of PKCδ expression using specific PKCδ siRNA significantly inhibited Docetaxel-induced activation of IRE1α and the JNK pathway. These findings provide new insights to understand the mode of action of taxanes in treatment of human melanoma.
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References
Rowinsky EK, Donehower RC (1991) The clinical pharmacology and use of antimicrotubule agents in cancer chemotherapeutics. Pharmacol Ther 52:35–84. doi:10.1016/0163-7258(91)90086-2
Mhaidat NM, Wang Y, Kiejda KA, Zhang XD, Hersey P (2007) Docetaxel-induced apoptosis in melanoma cells is dependent on activation of caspase-2. Mol Cancer Ther 6:752–761. doi:10.1158/1535-7163.MCT-06-0564
Mhaidat NM, Zhang XD, Jiang CC, Hersey P (2007) Docetaxel-induced apoptosis of human melanoma is mediated by activation of c-Jun NH2-terminal kinase and inhibited by the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 pathway. Clin Cancer Res 13:1308–1314. doi:10.1158/1078-0432.CCR-06-2216
Ellgaard L, Riek R, Herrmann T, Guntert P, Braun D, Helenius A, Wuthrich K (2001) NMR structure of the calreticulin P-domain. Proc Natl Acad Sci USA 98:3133–3138. doi:10.1073/pnas.051630098
Nawrocki S, Carew J, Dunner K, Boise L, Chiao P, Huang P, Abbruzzese J, McConkey D (2005) Bortezomib inhibits PKR-like endoplasmic reticulum (ER) kinase and induces apoptosis via ER stress in human pancreatic cancer cells. Cancer Res 65:11510–11519. doi:10.1158/0008-5472.CAN-05-2394
Ma Y, Hendershot LM (2004) The role of the unfolded protein response in tumour development: friend or foe? Nat Rev Cancer 4:966–977. doi:10.1038/nrc1505
Harding HP, Calfon M, Urano F, Novoa I, Ron D (2002) Transcriptional and translational control in the Mammalian unfolded protein response. Annu Rev Cell Dev Biol 18:575–599. doi:10.1146/annurev.cellbio.18.011402.160624
Schroder M, Kaufman RJ (2005) The mammalian unfolded protein response. Annu Rev Biochem 74:739–789. doi:10.1146/annurev.biochem.73.011303.074134
Urano F, Wang X, Bertolotti A et al (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287:664–666. doi:10.1126/science.287.5453.664
Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, Hori S, Kakizuka A, Ichijo H (2002) ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev 16:1345–1355. doi:10.1101/gad.992302
Hung C, Ichimura T, Stevens J, Bonventre J (2003) Protection of renal epithelial cells against oxidative injury by endoplasmic reticulum stress preconditioning is mediated by ERK1/2 activation. J Biol Chem 278:29317–29326. doi:10.1074/jbc.M302368200
Mhaidat NM, Thorne RF, Zhang XD, Hersey P (2007) Regulation of Docetaxel-induced apoptosis of human melanoma cells by different isoforms of protein kinase C. Mol Cancer Res 5:1073–1081. doi:10.1158/1541-7786.MCR-07-0059
Zhang XD, Borrow JM, Zhang XY, Nguyen T, Hersey P (2003) Activation of ERK1/2 protects melanoma cells from TRAIL-induced apoptosis by inhibiting Smac/DIABLO release from mitochondria. Oncogene 22:2869–2881. doi:10.1038/sj.onc.1206427
Shtill AA, Mandlekar S, Yu R et al (1999) Differential regulation of mitogen-activated protein kinases by microtubule-binding agents in human breast cancer cells. Oncogene 18:377–384. doi:10.1038/sj.onc.1202305
Kyriakis JM, Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807–869
Karin M (1995) The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270:16483–16486
Ferri K, Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat Cell Biol 3:255–263. doi:10.1038/ncb1101-e255
Tiwari M, Kumar A, Sinha RA et al (2006) Mechanism of 4-HPR-induced apoptosis in glioma cells: evidences suggesting role of mitochondrial-mediated pathway and endoplasmic reticulum stress. Carcinogenesis 10:2047–2058. doi:10.1093/carcin/bgl051
Yang Q, Kim Y, Lin Y, Lewis J, Neckers L, Liu Z (2006) Tumour necrosis factor receptor 1 mediates endoplasmic reticulum stress-induced activation of the MAP kinase JNK. EMBO Rep 7:622–627
Cheung HH, Lynn Kelly N, Liston P, Korneluk RG (2006) Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: a role for the IAPs. Exp Cell Res 312:2347–2357. doi:10.1016/j.yexcr.2006.03.027
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 67:9750–9761. doi:10.1158/0008-5472.CAN-07-2047
Hersey P, Zhang XD (2008) Adaptation to ER stress as a driver of malignancy and resistance to therapy in human melanoma. Pigment Cell Melanoma Res 21:358–367. doi:10.1111/j.1755-148X.2008.00467.x
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This work was supported by the NSW State Cancer Council, and the National Health and Medical Research Council, Australia.
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Mhaidat, N.M., Thorne, R., Zhang, X.D. et al. Involvement of endoplasmic reticulum stress in Docetaxel-induced JNK-dependent apoptosis of human melanoma. Apoptosis 13, 1505–1512 (2008). https://doi.org/10.1007/s10495-008-0276-8
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DOI: https://doi.org/10.1007/s10495-008-0276-8