BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells

Oncotarget

Volumn 6, Issue 32, 2015, Pages 33397-33409

  Ambrosini, Grazia ^a   Sawle, Ashley D ^a   Musi, Elgilda ^a   Schwartz, Gary K ^a  

^a Department of Medicine   (United States)

Author keywords

Bcl xL; BRD4; Gnaq 11; JQ1; Rad51

Indexed keywords

4 (4 CHLOROPHENYL) 2,3,9 TRIMETHYL 6H THIENO[3,2 F][1,2,4]TRIAZOLO[4,3 A][1,4]DIAZEPINE 6 ACETIC ACID TERT BUTYL ESTER; 8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; MEMBRANE PROTEIN; MYC PROTEIN; PROTEIN BCL XL; PROTEIN BRD4; RAD51 PROTEIN; SELUMETINIB; SOTRASTAURIN; UNCLASSIFIED DRUG; (+)-JQ1 COMPOUND; AZEPINE DERIVATIVE; BRD4 PROTEIN, MOUSE; GNA11 PROTEIN, HUMAN; GNAQ PROTEIN, HUMAN; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT; NUCLEAR PROTEIN; TRANSCRIPTION FACTOR; TRIAZOLE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL CYCLE REGULATION; CELL MEDIATED CYTOTOXICITY; CELL VIABILITY; CONTROLLED STUDY; DNA REPAIR; FEMALE; GENE CONTROL; GENE IDENTIFICATION; GENE MUTATION; MICROARRAY ANALYSIS; MOUSE; NONHUMAN; PROMOTER REGION; PROTEIN TARGETING; TREATMENT DURATION; TREATMENT RESPONSE; UVEA MELANOMA; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL DEATH; DRUG EFFECTS; DRUG SCREENING; GENETICS; HUMAN; MELANOMA; MOLECULARLY TARGETED THERAPY; ONCOGENE MYC; PATHOLOGY; PHYSIOLOGY; SCID MOUSE; TUMOR CELL CULTURE; UVEAL NEOPLASMS;

ANIMALS; AZEPINES; CELL DEATH; GENES, MYC; GTP-BINDING PROTEIN ALPHA SUBUNITS; GTP-BINDING PROTEIN ALPHA SUBUNITS, GQ-G11; HUMANS; MELANOMA; MICE; MICE, SCID; MOLECULAR TARGETED THERAPY; NUCLEAR PROTEINS; TRANSCRIPTION FACTORS; TRIAZOLES; TUMOR CELLS, CULTURED; UVEAL NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84946014028     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5179     Document Type: Article

References (44)

1. Dawson MA, Kouzarides T. Cancer Epigenetics: from mechanism to therapy. Cell. 2012; 150:12-27.
2. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, et al. Selective inhibition of BET bromodomains. Nature. 2010; 468:1067-1073.
3. Fu LL, Tian M, Li X, Li JJ, Huang J, Ouyang L, Zhang Y, Liu B. Inhibition of BET bromodomains as a therapeutic strategy for cancer drug discovery. Oncotarget. 2015; 6:5501-5516.
4. Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, BantscheffM, Chan WI, Robson SC, Chung CW, Hopf C, Savitski MM, Huthmacher C, Gudgin E, Lugo D, et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 2011; 478:529-533.
5. Jang MK, Mochizuki K, Zhou M, Jeong HS, Brady JN, Ozato K. The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol Cell. 2005; 19:523-534.
6. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J, Chesi M, Schinzel AC, McKeown MR, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011; 146:904-917.
7. 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.
8. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, Bergeron L, Sims RJ. Targeting MYC dependence in cancer by inhibiting BET bromodomains. PNAS USA. 2011; 108:16669-16674.
9. Barbieri I, Cannizzaro E, Dawson MA. Bromodomains as therapeutic targets in cancer. Brief Functional Genomics. 2013; 12:219-230.
10. Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, Rodig SJ, Kung AL, Bradner JE, Weinstock DM. BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012; 120:2843-2852.
11. Lockwood WW, Zejnullahu K, Bradner JE, Varmus H. Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins. PNAS USA. 2012; 109:19408-19413.
12. 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.
13. Bandopadhayay P, Bergthold G, Nguyen B, Schubert S, Gholamin S, Tang Y, Bolin S, Schumacher SE, Zeid R, Masoud S, Yu F, Vue N, Gibson WJ, et al. BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014; 20:912-925.
14. Segura MF, Fontanals-Cirera B, Gaziel-Sovran A, Guijarro MV, Hanniford D, Zhang G, GonzalezGomez P, Morante M, Jubierre L, Zhang W, Darvishian F, Ohlmeyer M, Osman I, et al. BRD4 sustains melanoma proliferation and represents a new target for epigenetic therapy. Cancer Res. 2013; 73:6264-6276.
15. Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Hawkins BS, Hayman JA, Jaiyesimi I, Jampol LM, Kirkwood JM, Koh WJ, Robertson DM, et al. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005; 123:1639-1643.
16. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, Simpson EM, Barsh GS, Bastian BC. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009; 457:599-602.
17. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, et al. Mutations in GNA11 in uveal melanoma. New England J Med. 2010; 363:2191-2199.
18. Singh AD, Bergman L, Seregard S. Uveal melanoma: epidemiologic aspects. Ophthalmol Clin N America. 2005; 18:75-84.
19. Patel M, Smyth E, Chapman PB, Wolchok JD, Schwartz GK, Abramson DH, Carvajal RD. Therapeutic implications of the emerging molecular biology of uveal melanoma. Clin Cancer Res. 2011; 17:2087-2100.
20. Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jockel KH, Becher R. Prognostic implications of monosomy 3 in uveal melanoma. Lancet. 1996; 347:1222-1225.
21. van den Bosch T, van Beek JG, Vaarwater J, Verdijk RM, Naus NC, Paridaens D, de Klein A, Kilic E. Higher percentage of FISH-determined monosomy 3 and 8q amplification in uveal melanoma cells relate to poor patient prognosis. Investig Ophthalmol & Visual Sci. 2012; 53:2668-2674.
22. Parrella P, Caballero OL, Sidransky D, Merbs SL. Detection of c-myc amplification in uveal melanoma by fluorescent in situ hybridization. Investig Ophthalmol & Visual Sci. 2001; 42:1679-1684.
23. Dang CV. MYC on the path to cancer. Cell. 2012; 149:22-35.
24. Royds JA, Sharrard RM, Parsons MA, Lawry J, Rees R, Cottam D, Wagner B, Rennie IG. C-myc oncogene expression in ocular melanomas. Graefe's Arch Clin Exper Ophthalmol. 1992; 230:366-371.
25. Yu X, Ambrosini G, Roszik J, Eterovic AK, StempkeHale K, Seftor EA, Chattopadhyay C, Grimm E, Carvajal RD, Hendrix MJ, Hodi FS, Schwartz GK, Woodman SE. Genetic Analysis of the 'Uveal Melanoma' C918 cell line reveals atypical BRAF and common KRAS mutations and single tandem repeat profile identical to the cutaneous melanoma C8161 cell line. Pigment Cell & Melanoma Res. 2014; 28:357-9.
26. Chen X, Wu Q, Tan L, Porter D, Jager MJ, Emery C, Bastian BC. Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations. Oncogene. 2014; 33:4724-4734.
27. Ambrosini G, Musi E, Ho AL, de Stanchina E, Schwartz GK. Inhibition of mutant GNAQ signaling in uveal melanoma induces AMPK-dependent autophagic cell death. Mol Cancer Ther. 2013; 12:768-776.
28. Khalili JS, Yu X, Wang J, Hayes BC, Davies MA, Lizee G, Esmaeli B, Woodman SE. Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ-and GNA11-dependent manner. Clin Cancer Res. 2012; 18:4345-4355.
29. Musi E, Ambrosini G, de Stanchina E, Schwartz GK. The phosphoinositide 3-kinase alpha selective inhibitor BYL719 enhances the effect of the protein kinase C inhibitor AEB071 in GNAQ/GNA11-mutant uveal melanoma cells. Mol Cancer Ther. 2014; 13:1044-1053.
30. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010; 70:440-446.
31. Ambrosini G, Pratilas CA, Qin LX, Tadi M, Surriga O, Carvajal RD, Schwartz GK. Identification of unique MEK-dependent genes in GNAQ mutant uveal melanoma involved in cell growth, tumor cell invasion, and MEK resistance. Clin Cancer Res. 2012; 18:3552-3561.
32. Gallagher SJ, Mijatov B, Gunatilake D, Tiffen JC, Gowrishankar K, Jin L, Pupo GM, Cullinane C, Prinjha RK, Smithers N, McArthur GA, Rizos H, Hersey P. The epigenetic regulator I-BET151 induces BIM-dependent apoptosis and cell cycle arrest of human melanoma cells. J Investig Dermatol. 2014; 134:2795-2805.
33. Nemati F, de Montrion C, Lang G, Kraus-Berthier L, Carita G, Sastre-Garau X, Berniard A, Vallerand D, Geneste O, de Plater L, Pierre A, Lockhart B, Desjardins L, et al. Targeting Bcl-2/Bcl-XL induces antitumor activity in uveal melanoma patient-derived xenografts. PloS One. 2014; 9:e80836.
34. Hine CM, Li H, Xie L, Mao Z, Seluanov A, Gorbunova V. Regulation of Rad51 promoter. Cell Cycle. 2014; 13:2038-2045.
35. Blom DJ, Mooy CM, Luyten GP, Kerkvliet S, Ouwerkerk I, Zwinderman AH, Schrier PI, Jager MJ. Inverse correlation between expression of HLA-B and c-myc in uveal melanoma. J Pathol. 1997; 181:75-79.
36. Giese K, Kingsley C, Kirshner JR, Grosschedl R. Assembly and function of a TCR alpha enhancer complex is dependent on LEF-1-induced DNA bending and multiple proteinprotein interactions. Genes & Develop. 1995; 9:995-1008.
37. Kim TK, Maniatis T. The mechanism of transcriptional synergy of an in vitro assembled interferon-beta enhanceosome. Mol Cell. 1997; 1:119-129.
38. Boi M, Gaudio E, Bonetti P, Kwee I, Bernasconi E, Tarantelli C, Rinaldi A, Testoni M, Cascione L, Ponzoni M, Mensah AA, Stathis A, Stussi G, et al. The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs. Clin Cancer Res. 2015; 21:1628-1638.
39. Picaud S, Da Costa D, Thanasopoulou A, Filippakopoulos P, Fish PV, Philpott M, Fedorov O, Brennan P, Bunnage ME, Owen DR, Bradner JE, Taniere P, O'Sullivan B, et al. PFI-1, a highly selective protein interaction inhibitor, targeting BET Bromodomains. Cancer Res. 2013; 73:3336-3346.
40. De Waard-Siebinga I, Blom DJ, Griffioen M, Schrier PI, Hoogendoorn E, Beverstock G, Danen EH, Jager MJ. Establishment and characterization of an uveal-melanoma cell line. Intern J Cancer. 1995; 62:155-161.
41. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004; 5:R80.
42. Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Gen Mol Biol. 2004; 3: Article3.
43. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B. 1995; 57:289-300.
44. Ambrosini G, Seelman SL, Qin LX, Schwartz GK. The cyclin-dependent kinase inhibitor flavopiridol potentiates the effects of topoisomerase I poisons by suppressing Rad51 expression in a p53-dependent manner. Cancer Res. 2008; 68:2312-2320.