The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells
The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells(388 views) Farina AR, Tacconelli A, Cappabianca L, Cea G, Chioda A, Romanelli A, Pensato S, Pedone C, Gulino A, Mackay AR
Oncogene (ISSN: 1476-5594, 0950-9232), 2009 Nov 19; 28(46): 4075-4094.
Keywords: Geldanamycin, Hsp90, Neuroblastoma, Trkai, Heat Shock Protein 90, Protein Tyrosine Kinase A, Alternative Rna Splicing, Apoptosis, Article, Cancer Inhibition, Carcinogenesis, Controlled Study, Endoplasmic Reticulum, Human, Human Cell, Neuroblastoma Cell, Priority Journal, Protein Analysis, Protein Function, Protein Protein Interaction, Alternative Splicing, Antigens, Surface, Benzoquinones, Enzyme Stability, Tumor Suppressor, Hsp90 Heat-Shock Proteins, Isoenzymes, Lactams, Macrocyclic, Oncogenes, Phosphorylation, Protein Binding, Protein Kinase Inhibitors, Protein Transport, Receptor, Transfection, Tumor Cells, Cultured,
Affiliations: *** IBB - CNR ***
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
Department of Biological Science, University of Naples Federico II, Naples, Italy
References: Arevalo, J.C., Conde, B., Hempstead, B.L., Chao, M.V., Martin-Zanca, D., Perez, P., TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of the receptor (2000) Mol Cell Biol, 20, pp. 5908-591
Bagatell, R., Gore, L., Egorin, M.J., Ho, R., Heller, G., Boucher, N., Phase i pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17- demethoxygeldanamycin in paediatric patients with recurrent or refractory solid tumors: A pediatric oncology experimental therapeutics investigators corsortium study (2007) Clin Cancer Res, 13, pp. 1783-1788
Becker, B., Mullhof, G., Farkas, B., Wild, P.J., Landthaler, M., Stoltz, W., Induction of Hsp90 protein expression in malignant melanomas and melanoma metastases (2004) Exp Dermatol, 13, pp. 27-32
Bijlmakers, M.J., Marsh, M., Hsp90 is essential for the synthesis and subsequent membrane association, but not the maintenance of the Src-kinase p56 (lck) (2000) Mol Biol Cell, 11, pp. 1585-1595
Citri, A., Harari, D., Shohat, G., Ramakrishnan, P., Gan, J., Lavi, S., Hsp90 recognises a common surface on client kinases (2006) J Biol Chem, 281, pp. 14361-14369
Connell, P., Ballinger, C.A., Jiang, J., Wu, Y., Thompson, J.L., Hohfeld, J., The co-chaperone CHIP regulates protein triage decisions mediated by heat shock proteins (2001) Nat Cell Biol, 3, pp. 93-96
Dai, C., Whitesell, L., HSP90: A rising star on the horizon of anticancer targets (2005) Future Oncol, 1, pp. 529-540
Eggert, A., Grotzer, M.A., Ikegaki, N., Liu, X.G., Evans, A.E., Broduer, G.M., Expression of the neurotrophin receptor TrkA down-regulates expression and function of angiogenic stimulators in SH-SY5Y neuroblastoma cells (2002) Cancer Res, 62, pp. 1802-1808
Erdmann, F., Jarczowski, F., Weiwad, M., Fischer, G., Edlich, F., Hsp90-mediated inhibition of FKBP38 regulates apoptosis in neuroblastoma cells (2007) FEBS Lett, 581, pp. 5709-5714
Escobar, M.A., Hoelz, D.J., Sandoval, J.A., Hickey, R.J., Grosfeld, J.L., Malkas, L.H., Profiling of nuclear extract proteins from human neuroblastoma cell lines: The search for fingerprints (2005) J Pediatr Surg, 40, pp. 349-358
Frey, S., Leskovar, A., Reinstein, J., Buchner, J., The ATPase cycle of the endoplasmic chaperone Grp94 (2007) J Biol Chem, 282, pp. 35612-35620
Geetha, T., Wooten, M.W., TrkA receptor endolysosomal degradation is both ubiquitin and proteosome dependent (2008) Traffic, 9, pp. 1146-1156
Graner, M.W., Bigner, D.D., Chaperone proteins and brain tumors: Potential targets and possible therapeutics (2005) Neuro Oncol, 7, pp. 260-277
Grem, J.L., Morrison, G., Guo, X.D., Agnew, E., Takimoto, C.H., Thomas, R., Phase i and pharmacologic study of 17-(allylamino)-17- demethoxygeldanamycin in adult patients with solid tumors (2005) J Clin Oncol, 23, pp. 1885-1893
Grenert, J.P., Johnson, B.D., Toft, D.O., The importance of ATP binding and hydrolysis by Hsp90 in formation and function of protein hetero-complexes (1999) J Biol Chem, 274, pp. 17525-17533
Grenert, J.P., Sullivan, W.P., Fadden, P., Haystead, T.A.J., Clark, J., Mimnaugh, E., The amino acid terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation (1997) J Biol Chem, 272, pp. 23843-23850
Jakob, U., Lilie, H., Meyer, I., Buchner, J., Transient interaction of Hsp90 with early unfolding intermediates of citrate synthase. Implications for heat shock in vivo (1995) J Biol Chem, 270, pp. 7288-7294
Jullien, J., Giuli, V., Reichardt, L.F., Rudkin, B.B., Molecular kinetics of nerve growth factor receptor trafficking and activation (2002) J Biol Chem, 277, pp. 38700-38708
Kim, S., Kang, J., Hu, W., Evers, B.M., Chung, D.H., Geldanamycin decreases Raf i and Akt levels and induces apoptosis in neuroblastomas (2003) Int J Cancer, 103, pp. 352-359
Lavenius, E., Gestblom, C., Johansson, I., Nanberg, E., Pahlman, S., Transfection of TrkA into human neuroblastoma cells restores ability to differentiate in response to nerve growth factor (1995) Cell Growth Differ, 6, pp. 727-736
Lavictoire, S.J., Parolin, D.A., Klimowicz, A.C., Kelly, J.F., Lorimer, I.A., Interaction of Hsp90 with the nascent form of the mutant epidermal growth factor receptor EGFRvIII (2003) J Biol Chem, 278, pp. 5292-5299
Lopez-Maderuelo, M.D., Fernandez-Renart, M., Maratilla, C., Renart, J., Opposite effects of the Hsp90 inhibitor geldanamycin: Induction of apoptosis in PC12, and differentiation in N2A cells (2001) FEBS Lett, 490, pp. 23-27
Lucarelli, E., Kaplan, D., Thiele, C.J., Activation of trk-A but not trk-B signal transduction inhibits growth of neuroblastoma cells (1997) Eur J Cancer, 33, pp. 2068-2070
Marcu, M.G., Doyle, M., Berlotti, A., Ron, D., Hendershot, L., Neckers, L., Heat shock protein 90 modulates the unfolded protein reponse by stabilising IRE1a (2002) Mol Cell Biol, 22, pp. 8506-8513
Marczin, N., Papapetropuolus, A., Catrovas, J.D., Tyrosine kinase inhibitors suppress endotoxin-and IL-1b-induced NO synthesis in aortic smooth muscle cells (1993) Am J Physiol, 265, pp. 34-43
Marques, C., Pereira, P., Taylor, F., Liang, J.N., Reddy, V.N., Szweda, L.I., Ubiquitin-dependent lysosomal degradation of the HNE-modified proteins in lens epithelial cells (2004) FASEB J, 18, pp. 1424-1426
Martin-Zanca, D., Oskam, R., Mitra, G., Copeland, T., Barbacid, M., Molecular and biochemical characterisation of the human trk proto-oncogene (1989) Mol Cell Biol, 9, pp. 24-33
Matei, D., Satpathy, M., Cao, L., Lai, Y.C., Nakashatri, H., Donner, D.B., The platelet derived growth factor receptor is destabilised by geldanamycins in cancer cells (2007) J Biol Chem, 282, pp. 445-453
Matsushima, H., Bogenmann, E., Nerve growth factor (NGF) induces neuronal differentiation in neuroblastoma cells transfected with the NGF receptor cDNA (1990) Mol Cell Biol, 10, pp. 5015-5020
Miyata, Y., The Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic agents (2005) Curr Pharm des, 11, pp. 1131-1138
Nakagawara, A., Trk receptor tyrosine kinase: A bridge between cancer and neural development (2001) Cancer Lett, 169, pp. 107-114
Nakagawara, A., Arima, M., Azar, C.G., Scavarda, N.J., Brodeur, G.M., Inverse relationship between trk expression and N-myc amplification in human neuroblastoma (1992) Cancer Res, 52, pp. 1364-1368
Nimmanapalli, R., O'Bryan, E., Kuhn, D., Yamaguchi, H., Wang, H.C., Bhalla, K.N., Regulation of 17-AAG-induced apoptosis: Role of Bcl-2, BclXl, and Bax downstream of 17-AAG-mediated down-regulation of Akt, Raf-1, and Src kinases (2003) Blood, 102, pp. 269-275
Neckers, L., Hsp90 inhibitors as novel cancer chemotherapeutic agents (2002) Trends Mol Med, 8, pp. S55-S61
Onuoha, S.C., Mukund, S.R., Coulstock, E.T., Sengerova, B., Shaw, J., McLaughlin, S.H., Mechanistic studies on Hsp90 inhibition by ansamycin derivatives (2007) J Mol Biol, 372, pp. 287-297
Orike, N., Middleton, G., Borthwick, E., Buchman, V., Cowen, T., Davies, A.M., Role of PI 3-kinase, Akt and Bcl-2-related proteins in sustaining the survival of neurotrophic factor-independent adult sympathetic neurons (2001) J Cell Biol, 154, pp. 995-1005
Pahlman, S., Hedborg, F., Development of the neural crest and sympathetic nervous system (2000) Neuroblastoma, pp. 9-19. , Brodeur GM, Sawada T, Tsuchida S, Voute PA (eds) Elsavier Press: Amestadam
Peng, X., Guo, X., Borkan, S.C., Bharti, A., Kuramochi, Y., Calderwood, S., Heat shock protein 90 stabilisation of ErbB2 expression is disrupted by ATP depletion in myocytes (2005) J Biol Chem, 280, pp. 13148-13152
Puyo, S., La Morvan, V., Robert, J., Impact of EGFR gene polymorphisms on anticancer drug cytotoxicity in vitro (2008) Mol Diagn Ther, 12, pp. 225-234
Ramanathan, R.K., Egorin, M.J., Eisenman, J.L., Ramalingham, S., Fried-Land, D., Agarwala, S.S., Phase i and pharmacodynamic study of 17-(allylamino)-17- demethoxygeldanamycin in adult patients with refractory advanced cancers (2007) Clin Cancer Res, 13, pp. 1769-1774
Rao, R.V., Peel, A., Logvinova, A., Del Rio, G., Hermel, E., Yokata, T., Coupling endoplasmic reticulum stress to the cell death program: Role of the ER chaperone GRP78 (2002) FEBS Lett, 514, pp. 122-128
Richter, K., Muschler, P., Hainzl, O., Buchner, J., Coordinated ATP hydrolysis by the Hsp90 dimer (2001) J Biol Chem, 276, pp. 33689-33696
Rosser, M.F., Trotta, B.M., Marshall, M.R., Berwin, B., Nicchitta, C.V., Adenosine nucleotides and the regulation of GRP94-client protein interaction (2004) Biochemistry, 43, pp. 8835-8845
Scheibel, T., Weikl, T., Buchner, J., Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence (1998) Proc Natl Acad Sci USA, 95, pp. 1495-1499
Schneider, C., Sepp-Lorenzino, L., Nimmesgern, E., Ouerfelli, O., Danishefsky, S., Rosen, N., Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90 (1996) Proc Natl Acad Sci USA, 93, pp. 14536-14541
Schroder, M., Endoplasmic reticulum stress response (2008) Cell Mol Life Sci, 65, pp. 862-894
Shankovich, R., Shue, G., Kohtz, S.D., Conformational activation of a basic-helix-loop-helix protein (MyoD1) by the c-terminal region of murine Hsp90 (Hsp84) (1992) Mol Cell Biol, 12, pp. 5059-5068
Shen, J.H., Zhang, Y., Wu, N.H., Shen, Y.F., Resistance to geldanamycin-induced apoptosis in differentiated neuroblastoma SH-SY5Y cells (2007) Neurosci Lett, 414, pp. 110-114
Sidera, K., Gaitanou, M., Stellas, D., Matsas, R., Patsavoudi, E., A critical role for Hsp90 in cancer cell invasion involves interaction with the extracellular domain of HER-2 (2008) J Biol Chem, 283, pp. 2031-2041
Sidera, K., Samiotaki, M., Yfanti, E., Panayotou, G., Patsavoudi, E., Involvement of cell surface Hsp90 in cell migration reveals a role in the developing nervous system (2004) J Biol Chem, 279, pp. 45379-45388
Solit, D.B., Ivy, S.P., Kopil, C., Sikorski, R., Morris, M.J., Slovin, S.F., Phase i trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer (2007) Clin Cancer Res, 13, pp. 1775-1782
Stebbins, C.E., Russo, A.A., Schneider, C., Rosen, N., Hartl, F.U., Pavletich, N.P., Crystal structure of an Hsp90-geldanamycin complex: Targeting of a protein chaperone by an antitumor agents (1997) Cell, 89, pp. 239-250
Tacconelli, A., Farina, A.R., Cappabianca, L., Cea, G., Chioda, A., Panella, S., Alternative TrkA splicing and cancer (2006) Alternative Splicing in Cancer, pp. 67-87. , Venables JP (ed) Transworld Research Network Press: Kerala, India
Theodoraki, M.A., Kunjappu, M., Sternberg, D.W., Caplan, A.J., Akt shows variable sensitivity to an Hsp90 inhibitor depending on cell context (2007) Exp Cell Res, 313, pp. 3851-3858
Vega, V.L., De Maio, A., Geldanamycin treatment ameliorates the response to LPS in murine macrophages by decreasing CD14 surface expression (2003) Mol Biol Cell, 14, pp. 764-773
Wang, Y., Shen, J., Arenzana, N., Tirasophan, W., Kaufman, R.J., Pyrwes, R., Activation of ATF6 and an ATF6 binding site by the endoplasmic reticulum stress response (2000) J Biol Chem, 275, pp. 27013-27020
Watson, F.L., Porcionatto, M.A., Bhattacharryya, A., Stiles, C.D., Segal, R.A., TrkA glycosylation regulates receptor localisation and activity (1999) J Neurobiol, 39, pp. 323-326
Weigel, B.J., Blaney, S.M., Reid, J.M., Safgren, S.L., Bagatell, R., Kersey, J., A phase i study of 17-allyaminogeldanamycin in relapsed/refractory pediatric patients with solid tumors: A Chil-drens' Oncology Group study (2007) Clin Cancer Res, 13, pp. 1789-1793
Xu, W., Marcu, M., Yuan, X., Mimnaugh, E., Patterson, C., Neckers, L., Chaperon-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu (2002) Proc Natl Acad Sci USA, 99, pp. 12847-12852
Xu, W., Mimnaugh, E., Rosser, M.F.N., Nicchitta, C., Marcu, M., Yarden, Y., Sensitivity of mature ErbB2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90 (2001) J Biol Chem, 276, pp. 3702-3708
Xu, W., Neckers, L., Targeting the molecular chaperone heat shock protein 90 provides a multifaceted effect on diverse cell signalling pathways of cancer cells (2007) Clin Cancer Res, 13, pp. 1625-1629
Yoshimura, S., Nakamura, N., Barr, F., Misuri, Y., Ikehara, Y., Ohno, H., Direct targeting of cis-Golgi matrix proteins to the Golgi apparatus (2001) J Cell Sci, 114, pp. 4105-4115
Zhou, P., Fernandes, N., Dodge, I.L., Reddi, A.L., Rao, N., Safran, H., ErbB2 degradation mediated by the co-chaperone protein CHIP (2003) J Biol Chem, 278, pp. 13829-13837
The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells
Hsp90 chaperones stabilize many tyrosine kinases including several oncogenes, which are inhibited or induced to degrade by the Hsp90 inhibitor geldanamycin (GA). As a consequence, GA has been developed for future chemotherapeutic use in several tumour types including neuroblastoma (NB). Alternative splicing of the neurotrophin receptor tyrosine kinase TrkA may have a pivotal function in regulating NB behaviour, with reports suggesting that tumour-suppressing signals from TrkA may be converted to oncogenic signals by stress-regulated alternative TrkAIII splicing. Within this context, it is important to know whether Hsp90 interacts with TrkA variants in NB cells and how GA influences this. Here, we report that both TrkAI and TrkAIII are Hsp90 clients in human NB cells. TrkAI exhibits GA-sensitive interaction with Hsp90 required for receptor endoplasmic reticulum export, maturation, cell surface stabilization and ligand-mediated activation, whereas TrkAIII exhibits GA-sensitive interactions with Hsp90 required for spontaneous activity and to a lesser extent stability. We show that GA inhibits proliferation and induces apoptosis of TrkAI expressing NB cells, whereas TrkAIII reduces the sensitivity of NB cells to GA-induced elimination. Our data suggest that GA-sensitive interactions with Hsp90 are critical for both TrkAI tumour suppressor and TrkAIII oncogenic function in NB and that TrkAIII expression exerts a negative impact on GA-induced NB cell eradication, which can be counteracted by a novel TrkAIII-specific peptide nucleic acid inhibitor.
The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells
No results.
The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells