Mitochondrial matrix chaperone and c-myc inhibition causes enhanced lethality in glioblastoma

Oncotarget

Volumn 8, Issue 23, 2017, Pages 37140-37153

  Ishida, Chiaki Tsuge ^a   Shu, Chang ^a   Halatsch, Marc Eric ^b   Westhoff, Mike Andrew ^b   Altieri, Dario C ^c   Karpel Massler, Georg ^b   Siegelin, Markus David ^a  

^a Department of Medicine   (United States)

^b UNIVERSITY HOSPITAL ULM   (Germany)

^c WISTAR INSTITUTE   (United States)

Author keywords

Apoptosis; C myc; Gamitrinib; JQ1; OTX015

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; ANTINEOPLASTIC AGENT; BIM PROTEIN; BIRABRESIB; CHAPERONE; DEUBIQUITINASE; DEUBIQUITINASE USP9X; GAMITRINIB; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; INITIATION FACTOR 2ALPHA; MYC PROTEIN; PROTEIN BAK; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1; PROTEIN NOXA; UNCLASSIFIED DRUG; (+)-JQ1 COMPOUND; ACETANILIDE DERIVATIVE; AZEPINE DERIVATIVE; FUSED HETEROCYCLIC RINGS; GAMITRINIB-G4; GUANIDINE DERIVATIVE; HEAT SHOCK PROTEIN; MACROCYCLIC LACTAM; MITOCHONDRIAL PROTEIN; TRIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; DNA FRAGMENTATION; DOWN REGULATION; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVATION; GLIOBLASTOMA; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LETHALITY; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SINGLE DRUG DOSE; UPREGULATION; ANIMAL; CELL SURVIVAL; DRUG EFFECT; DRUG SCREENING; GENETICS; METABOLISM; MITOCHONDRION; NUDE MOUSE; RNA INTERFERENCE; TUMOR CELL LINE;

ACETANILIDES; ANIMALS; AZEPINES; CELL LINE, TUMOR; CELL SURVIVAL; ENDOPLASMIC RETICULUM CHAPERONE BIP; GLIOBLASTOMA; GUANIDINES; HEAT-SHOCK PROTEINS; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; LACTAMS, MACROCYCLIC; MICE, NUDE; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; MOLECULAR CHAPERONES; PROTO-ONCOGENE PROTEINS C-MYC; RNA INTERFERENCE; TRIAZOLES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85020180707     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.16202     Document Type: Article

References (53)

1. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005; 352:997-1003
2. Wei W, Shin YS, Xue M, Matsutani T, Masui K, Yang H, Ikegami S, Gu Y, Herrmann K, Johnson D, Ding X, Hwang K, Kim J, et al. Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma. Cancer Cell. 2016; 29:563-573
3. Cheng Z, Gong Y, Ma Y, Lu K, Lu X, Pierce LA, Thompson RC, Muller S, Knapp S, Wang J. Inhibition of BET bromodomain targets genetically diverse glioblastoma. Clin Cancer Res. 2013; 19:1748-1759
4. Berenguer-Daize C, Astorgues-Xerri L, Odore E, Cayol M, Cvitkovic E, Noel K, Bekradda M, MacKenzie S, Rezai K, Lokiec F, Riveiro ME, Ouafik L. OTX015 (MK-8628), a novel BET inhibitor, displays in vitro and in vivo antitumor effects alone and in combination with conventional therapies in glioblastoma models. Int J Cancer. 2016; 139:2047-2055
5. Toyoshima M, Howie HL, Imakura M, Walsh RM, Annis JE, Chang AN, Frazier J, Chau BN, Loboda A, Linsley PS, Cleary MA, Park JR, Grandori C. Functional genomics identifies therapeutic targets for MYC-driven cancer. Proc Natl Acad Sci USA. 2012; 109:9545-9550
6. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, Magoon D, Qi J, Blatt K, Wunderlich M, Taylor MJ, Johns C, Chicas A, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011; 478:524-528
7. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, Bergeron L, Sims RJ, 3rd. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA. 2011; 108:16669-16674
8. Chae YC, Caino MC, Lisanti S, Ghosh JC, Dohi T, Danial NN, Villanueva J, Ferrero S, Vaira V, Santambrogio L, Bosari S, Languino LR, Herlyn M, et al. Control of tumor bioenergetics and survival stress signaling by mitochondrial HSP90s. Cancer cell. 2012; 22:331-344
9. Kang BH, Siegelin MD, Plescia J, Raskett CM, Garlick DS, Dohi T, Lian JB, Stein GS, Languino LR, Altieri DC. Preclinical characterization of mitochondria-targeted small molecule hsp90 inhibitors, gamitrinibs, in advanced prostate cancer. Clin Cancer Res. 2010; 16:4779-4788
10. Siegelin MD, Dohi T, Raskett CM, Orlowski GM, Powers CM, Gilbert CA, Ross AH, Plescia J, Altieri DC. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. J Clin Invest. 2011; 121:1349-1360
11. Kang BH, Plescia J, Song HY, Meli M, Colombo G, Beebe K, Scroggins B, Neckers L, Altieri DC. Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90. J Clin Invest. 2009; 119:454-464
12. Kang BH, Plescia J, Dohi T, Rosa J, Doxsey SJ, Altieri DC. Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network. Cell. 2007; 131:257-270
13. Fels DR, Koumenis C. The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer biology & therapy. 2006; 5:723-728
14. Kline CL, Van den Heuvel AP, Allen JE, Prabhu VV, Dicker DT, El-Deiry WS. ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2alpha kinases. Sci Signal. 2016; 9:ra18
15. Fang X, Zhou W, Wu Q, Huang Z, Shi Y, Yang K, Chen C, Xie Q, Mack SC, Wang X, Carcaboso AM, Sloan AE, Ouyang G, et al. Deubiquitinase USP13 maintains glioblastoma stem cells by antagonizing FBXL14-mediated Myc ubiquitination. J Exp Med. 2017; 214:245-267
16. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003; 63:5821-5828
17. Wang J, Wang H, Li Z, Wu Q, Lathia JD, McLendon RE, Hjelmeland AB, Rich JN. c-Myc is required for maintenance of glioma cancer stem cells. PLoS One. 2008; 3:e3769
18. Du H, Wolf J, Schafer B, Moldoveanu T, Chipuk JE, Kuwana T. BH3 domains other than Bim and Bid can directly activate Bax/Bak. The Journal of biological chemistry. 2011; 286:491-501
19. Karpel-Massler G, Shu C, Chau L, Banu M, Halatsch ME, Westhoff MA, Ramirez Y, Ross AH, Bruce JN, Canoll P, Siegelin MD. Combined inhibition of Bcl-2/Bcl-xL and Usp9X/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo. Oncotarget. 2015; 6:14507-21. doi: 10.18632/oncotarget.3993
20. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005; 435:677-6 81
21. Tagscherer KE, Fassl A, Campos B, Farhadi M, Kraemer A, Bock BC, Macher-Goeppinger S, Radlwimmer B, Wiestler OD, Herold-Mende C, Roth W. Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene. 2008; 27:6646-6 656
22. Dai H, Meng XW, Kaufmann SH. Mitochondrial apoptosis and BH3 mimetics. F1000Res. 2016; 5:2804
23. Elgendy M, Abdel-Aziz AK, Renne SL, Bornaghi V, Procopio G, Colecchia M, Kanesvaran R, Toh CK, Bossi D, Pallavicini I, Perez-Gracia JL, Lozano MD, Giandomenico V, et al. Dual modulation of MCL-1 and mTOR determines the response to sunitinib. J Clin Invest. 2016
24. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010; 463:899-905
25. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ, Huang DC, Hymowitz SG, Jin S, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013; 19:202-2 08
26. Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, Puvvada SD, Wendtner CM, Roberts AW, Jurczak W, Mulligan SP, Bottcher S, Mobasher M, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016; 17:768-7 78
27. Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, Carney DA, He SZ, Huang DC, Xiong H, Cui Y, Busman TA, McKeegan EM, et al. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2012; 30:488-496
28. Mason KD, Carpinelli MR, Fletcher JI, Collinge JE, Hilton AA, Ellis S, Kelly PN, Ekert PG, Metcalf D, Roberts AW, Huang DC, Kile BT. Programmed anuclear cell death delimits platelet life span. Cell. 2007; 128:1173-1186
29. Bagheri-Yarmand R, Sinha KM, Gururaj AE, Ahmed Z, Rizvi YQ, Huang SC, Ladbury JE, Bogler O, Williams MD, Cote GJ, Gagel RF. A novel dual kinase function of the RET proto-oncogene negatively regulates activating transcription factor 4-mediated apoptosis. The Journal of biological chemistry. 2015; 290:11749-11761
30. Singleton DC, Harris AL. Targeting the ATF4 pathway in cancer therapy. Expert Opin Ther Targets. 2012; 16:1189-1202
31. Dey S, Sayers CM, Verginadis, II, Lehman SL, Cheng Y, Cerniglia GJ, Tuttle SW, Feldman MD, Zhang PJ, Fuchs SY, Diehl JA, Koumenis C. ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis. J Clin Invest. 2015; 125:2592-2608
32. Ye J, Kumanova M, Hart LS, Sloane K, Zhang H, De Panis DN, Bobrovnikova-Marjon E, Diehl JA, Ron D, Koumenis C. The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. EMBO J. 2010; 29:2082-2096
33. Wang Q, Mora-Jensen H, Weniger MA, Perez-Galan P, Wolford C, Hai T, Ron D, Chen W, Trenkle W, Wiestner A, Ye Y. ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc Natl Acad Sci U S A. 2009; 106:2200-2205
34. Qing G, Li B, Vu A, Skuli N, Walton ZE, Liu X, Mayes PA, Wise DR, Thompson CB, Maris JM, Hogarty MD, Simon MC. ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell. 2012; 22:631-644
35. Fawcett TW, Martindale JL, Guyton KZ, Hai T, Holbrook NJ. Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT/enhancer-binding protein (C/EBP)-ATF composite site to regulate Gadd153 expression during the stress response. Biochem J. 1999; 339:135-141
36. Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2002; 2:183-192
37. Faber AC, Ebi H, Costa C, Engelman JA. Apoptosis in targeted therapy responses: the role of BIM. Adv Pharmacol. 2012; 65:519-542
38. Hata AN, Engelman JA, Faber AC. The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics. Cancer Discov. 2015; 5:475-487
39. Tarrado-Castellarnau M, de Atauri P, Cascante M. Oncogenic regulation of tumor metabolic reprogramming. Oncotarget. 2016; 7:62726-53. doi: 10.18632/oncotarget.10911
40. Sheng Z, Li L, Zhu LJ, Smith TW, Demers A, Ross AH, Moser RP, Green MR. A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nat Med. 2010; 16:671-677
41. Karpel-Massler G, Bâ M, Shu C, Halatsch ME, Westhoff MA, Bruce JN, Canoll P, Siegelin MD. TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo. Oncotarget. 2015; 6:36456-71. doi: 10.18632/oncotarget.5505
42. Karpel-Massler G, Kast RE, Westhoff MA, Dwucet A, Welscher N, Nonnenmacher L, Hlavac M, Siegelin MD, Wirtz CR, Debatin KM, Halatsch ME. Olanzapine inhibits proliferation, migration and anchorage-independent growth in human glioblastoma cell lines and enhances temozolomide's antiproliferative effect. J Neurooncol. 2015; 122:21-33
43. Ghosh JC, Siegelin MD, Vaira V, Faversani A, Tavecchio M, Chae YC, Lisanti S, Rampini P, Giroda M, Caino MC, Seo JH, Kossenkov AV, Michalek RD, et al. Adaptive mitochondrial reprogramming and resistance to PI3K therapy. J Natl Cancer Inst. 2015; 107
44. Karpel-Massler G, Westhoff MA, Kast RE, Dwucet A, Nonnenmacher L, Wirtz CR, Debatin KM, Halatsch ME. Artesunate enhances the antiproliferative effect of temozolomide on U87MG and A172 glioblastoma cell lines. Anticancer Agents Med Chem. 2014; 14:313-318
45. Karpel-Massler G, Banu MA, Shu C, Halatsch ME, Westhoff MA, Bruce JN, Canoll P, Siegelin MD. Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo. Oncotarget. 2016; 7:12791-805. doi: 10.18632/oncotarget.7302
46. Karpel-Massler G, Pareja F, Aime P, Shu C, Chau L, Westhoff MA, Halatsch ME, Crary JF, Canoll P, Siegelin MD. PARP inhibition restores extrinsic apoptotic sensitivity in glioblastoma. PLoS One. 2014; 9:e114583
47. Karpel-Massler G, Horst BA, Shu C, Chau L, Tsujiuchi T, Bruce JN, Canoll P, Greene LA, Angelastro JM, Siegelin MD. A Synthetic Cell-Penetrating Dominant-Negative ATF5 Peptide Exerts Anticancer Activity against a Broad Spectrum of Treatment-Resistant Cancers. Clin Cancer Res. 2016
48. Karpel-Massler G, Ramani D, Shu C, Halatsch ME, Westhoff MA, Bruce JN, Canoll P, Siegelin MD. Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo. Oncotarget. 2016; 7:33512-28. doi: 10.18632/oncotarget.9257
49. Preuss E, Hugle M, Reimann R, Schlecht M, Fulda S. Pan-mammalian target of rapamycin (mTOR) inhibitor AZD8055 primes rhabdomyosarcoma cells for ABT-737-induced apoptosis by down-regulating Mcl-1 protein. The Journal of biological chemistry. 2013; 288:35287-35296
50. Antonietti P, Linder B, Hehlgans S, Mildenberger IC, Burger MC, Fulda S, Steinbach JP, Gessler F, Rodel F, Mittelbronn M, Kogel D. Interference with the HSF1/HSP70/BAG3 pathway primes glioma cells to matrix detachment and BH3 mimetic-induced apoptosis. Mol Cancer Ther. 2016
51. Karpel-Massler G, Horst BA, Shu C, Chau L, Tsujiuchi T, Bruce JN, Canoll P, Greene LA, Angelastro JM, Siegelin MD. A Synthetic Cell-Penetrating Dominant-Negative ATF5 Peptide Exerts Anticancer Activity against a Broad Spectrum of Treatment-Resistant Cancers. Clin Cancer Res. 2016; 22:4698-4711
52. Karpel-Massler G, Ramani D, Shu C, Halatsch ME, Westhoff MA, Bruce JN, Canoll P, Siegelin MD. Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo. Oncotarget. 2016; 7:33512-33528
53. Pareja F, Macleod D, Shu C, Crary JF, Canoll PD, Ross AH, Siegelin MD. PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD. Mol Cancer Res. 2014; 12:987-1001