Combined inhibition of Bcl-2/Bcl-xl and Usp9x/Bag3 overcomes apoptotic resistance in glioblastoma in vitro and in vivo

Oncotarget

Volumn 6, Issue 16, 2015, Pages 14507-14521

  Karpel Massler, Georg ^a   Shu, Chang ^a   Chau, Lily ^a   Banu, Matei ^a   Halatsch, Marc Eric ^b   Westhoff, Mike Andrew ^b   Ramirez, Yulian ^c   Ross, Alonzo H ^c   Bruce, Jeffrey N ^a   Canoll, Peter ^a   Siegelin, Markus D ^a  

^a Department of Medicine   (United States)

^b UNIVERSITY HOSPITAL ULM   (Germany)

^c UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

Abt263; Apoptotic resistance; BH3 mimetic; Glioblastoma; Gx15 070

Indexed keywords

NAVITOCLAX; OBATOCLAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1; APOPTOSIS REGULATORY PROTEIN; BAG3 PROTEIN, MOUSE; PROTEIN BCL X; PROTEINASE; SIGNAL TRANSDUCING ADAPTOR PROTEIN; USP9X PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CELL PROLIFERATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG STRUCTURE; GLIOBLASTOMA; GLIOBLASTOMA CELL LINE; IN VITRO STUDY; IN VIVO STUDY; MITOCHONDRIAL MEMBRANE POTENTIAL; MOUSE; NONHUMAN; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN PROCESSING; UPREGULATION; ANIMAL; BRAIN TUMOR; CHEMICAL STRUCTURE; DRUG RESISTANCE; DRUG SCREENING; GENETIC TRANSFECTION; GENETICS; HUMAN; METABOLISM; SCID MOUSE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; APOPTOSIS REGULATORY PROTEINS; BCL-X PROTEIN; BRAIN NEOPLASMS; DRUG RESISTANCE, NEOPLASM; ENDOPEPTIDASES; GLIOBLASTOMA; HUMANS; IN VITRO TECHNIQUES; MICE; MICE, SCID; MOLECULAR STRUCTURE; PROTO-ONCOGENE PROTEINS C-BCL-2; TRANSFECTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84931075379     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.3993     Document Type: Article

References (39)

1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma The New England journal of medicine. 2005; 352:987-996.
2. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L and Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. The New England journal of medicine. 2014; 370:709-722.
3. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. The New England journal of medicine. 2014; 370:699-708.
4. Karpel-Massler G, Westhoff MA, Kast RE, Wirtz CR and Halatsch ME. Erlotinib in glioblastoma: lost in translation? Anti-cancer agents in medicinal chemistry. 2011; 11:748-755.
5. van den Bent MJ, Brandes AA, Rampling R, Kouwenhoven MC, Kros JM, Carpentier AF, Clement PM, Frenay M, Campone M, Baurain JF, Armand JP, Taphoorn MJ, Tosoni A, Kletzl H, Klughammer B, Lacombe D, et al. Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2009; 27:1268-1274.
6. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suva ML, Regev A and Bernstein BE. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014; 344:1396-1401.
7. Davids MS and Letai A. Targeting the B-cell lymphoma/leukemia 2 family in cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2012; 30:3127-3135.
8. Yip KW and Reed JC. Bcl-2 family proteins and cancer. Oncogene. 2008; 27:6398-6406.
9. Konopleva M, Contractor R, Tsao T, Samudio I, Ruvolo PP, Kitada S, Deng X, Zhai D, Shi YX, Sneed T, Verhaegen M, Soengas M, Ruvolo VR, McQueen T, Schober WD, Watt JC, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer cell. 2006; 10:375-388.
10. van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, Czabotar PE, Willis SN, Scott CL, Day CL, Cory S, Adams JM, Roberts AW and Huang DC. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer cell. 2006; 10:389-399.
11. Nguyen M, Marcellus RC, Roulston A, Watson M, Serfass L, Murthy Madiraju SR, Goulet D, Viallet J, Belec L, Billot X, Acoca S, Purisima E, Wiegmans A, Cluse L, Johnstone RW, Beauparlant P, et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104:19512-19517.
12. Boiani M, Daniel C, Liu X, Hogarty MD and Marnett LJ. The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. The Journal of biological chemistry. 2013; 288:6980-6990.
13. Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, Maecker H, O'Rourke K, Bazan F, Eastham- Anderson J, Yue P, Dornan D, Huang DC and Dixit VM. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 2010; 463:103-107.
14. Hanahan D and Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646-674.
15. Gandhi L, Camidge DR, Ribeiro de Oliveira M, Bonomi P, Gandara D, Khaira D, Hann CL, McKeegan EM, Litvinovich E, Hemken PM, Dive C, Enschede SH, Nolan C, Chiu YL, Busman T, Xiong H, et al. Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncology. 2011; 29:909-916.
16. 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, Krivoshik AP, Enschede SH and Humerickhouse R. 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 Clinical Oncology. 2011; 30:488-496.
17. Wilson WH, O'Connor OA, Czuczman MS, LaCasce AS, Gerecitano JF, Leonard JP, Tulpule A, Dunleavy K, Xiong H, Chiu YL, Cui Y, Busman T, Elmore SW, Rosenberg SH, Krivoshik AP, Enschede SH, et al. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncology. 2010; 11:1149-1159.
18. Kipps TJ, Eradat H, Grosicki S, Catalano J, Cosolo W, Dyagil I, Yalamanchili S, Chai A, Saharanaman S, Punnoose E, Hurst D and Pylypenko H. A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia. Leuk Lymphoma. 2015:1-30.
19. Chiappori A, Williams C, Northfelt DW, Adams JW, Malik S, Edelman MJ, Rosen P, Van Echo DA, Berger MS and Haura EB. Obatoclax mesylate, a pan-bcl-2 inhibitor, in combination with docetaxel in a phase 1/2 trial in relapsed non-small-cell lung cancer. J Thorac Oncology. 2014; 9:121-125.
20. Chiappori AA, Schreeder MT, Moezi MM, Stephenson JJ, Blakely J, Salgia R, Chu QS, Ross HJ, Subramaniam DS, Schnyder J and Berger MS. A phase I trial of pan- Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer. Br J Cancer. 2012; 106:839-845.
21. Hwang JJ, Kuruvilla J, Mendelson D, Pishvaian MJ, Deeken JF, Siu LL, Berger MS, Viallet J and Marshall JL. Phase I dose finding studies of obatoclax (GX15-070), a small molecule pan-BCL-2 family antagonist, in patients with advanced solid tumors or lymphoma. Clinical Cancer Research. 2010; 16:4038-4045.
22. Paik PK, Rudin CM, Pietanza MC, Brown A, Rizvi NA, Takebe N, Travis W, James L, Ginsberg MS, Juergens R, Markus S, Tyson L, Subzwari S, Kris MG and Krug LM. A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer. Lung Cancer. 2011; 74:481-485.
23. Mattoo AR, Zhang J, Espinoza LA and Jessup JM. Inhibition of NANOG/NANOGP8 downregulates MCL- 1 in colorectal cancer cells and enhances the therapeutic efficacy of BH3 mimetics. Clinical cancer research: an official journal of the American Association for Cancer Research. 2014; 20:5446-5455.
24. Sun JG, Xiang J, Zeng XL, Li X, Wu P, Fung KP and Liu FY. Clitocine induces apoptosis and enhances the lethality of ABT-737 in human colon cancer cells by disrupting the interaction of Mcl-1 and Bak. Cancer letters. 2014; 355:253-263.
25. Preuss E, Hugle M, Reimann R, Schlecht M and 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.
26. Rahmani M, Aust MM, Attkisson E, Williams DC, Jr., Ferreira-Gonzalez A and Grant S. Dual inhibition of Bcl- 2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3-and Bim-dependent mechanism. Cancer research. 2013; 73:1340-1351.
27. Pareja F, Macleod D, Shu C, Crary JF, Canoll PD, Ross AH and Siegelin MD. PI3K and Bcl-2 inhibition primes glioblastoma cells to apoptosis through downregulation of Mcl-1 and Phospho-BAD. Molecular cancer research: 2014; 12:987-1001.
28. Sheng Z, Li L, Zhu LJ, Smith TW, Demers A, Ross AH, Moser RP and Green MR. A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nature medicine. 2010; 16:671-677.
29. Zhong Q, Gao W, Du F and Wang X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell. 2005; 121:1085-1095.
30. Festa M, Del Valle L, Khalili K, Franco R, Scognamiglio G, Graziano V, De Laurenzi V, Turco MC and Rosati A. BAG3 protein is overexpressed in human glioblastoma and is a potential target for therapy. The American journal of pathology. 2011; 178:2504-2512.
31. Peng J, Hu Q, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Wei W, Liu S and Wang H. USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma. Diagnostic pathology. 2013; 8:177.
32. Stegeman S, Jolly LA, Premarathne S, Gecz J, Richards LJ, Mackay-Sim A and Wood SA. Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFbeta-mediated axonogenesis. PloS one. 2013; 8:e68287.
33. Cox JL, Wilder PJ, Gilmore JM, Wuebben EL, Washburn MP and Rizzino A. The SOX2-interactome in brain cancer cells identifies the requirement of MSI2 and USP9X for the growth of brain tumor cells. PloS one. 2013; 8:e62857.
34. Wang S, Kollipara RK, Srivastava N, Li R, Ravindranathan P, Hernandez E, Freeman E, Humphries CG, Kapur P, Lotan Y, Fazli L, Gleave ME, Plymate SR, Raj GV, Hsieh JT and Kittler R. Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111:4251-4256.
35. Elgendy M, Ciro M, Abdel-Aziz AK, Belmonte G, Zuffo RD, Mercurio C, Miracco C, Lanfrancone L, Foiani M and Minucci S. Beclin 1 restrains tumorigenesis through Mcl- 1 destabilization in an autophagy-independent reciprocal manner. Nature communications. 2014; 5:5637.
36. Jane EP, Premkumar DR, DiDomenico JD, Hu B, Cheng SY and Pollack IF. YM-155 potentiates the effect of ABT- 737 in malignant human glioma cells via survivin and Mcl-1 downregulation in an EGFR-dependent context. Molecular Cancer Therapy. 2013; 12:326-338.
37. Karpel-Massler G, Westhoff MA, Zhou S, Nonnenmacher L, Dwucet A, Kast RE, Bachem MG, Wirtz CR, Debatin KM and Halatsch ME. Combined inhibition of HER1/EGFR and RAC1 results in a synergistic antiproliferative effect on established and primary cultured human glioblastoma cells. Molecular cancer therapeutics. 2013; 12:1783-1795.
38. Siegelin MD, Dohi T, Raskett CM, Orlowski GM, Powers CM, Gilbert CA, Ross AH, Plescia J and Altieri DC. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. The journal of clinical investigation. 2011; 121:1349-1360.
39. Karpel-Massler G, Pareja F, Aime P, Shu C, Chau L, Westhoff M, Halatsch M, Crary JF, Canoll P and Siegelin MD. PARP Inhibition Restores Extrinsic Apoptotic Sensitivity in Glioblastoma. PloS one. 2014; 9:e114583