BRD4 connects enhancer remodeling to senescence immune surveillance

Cancer Discovery

Volumn 6, Issue 6, 2016, Pages 613-629

  Tasdemir, Nilgun ^a,b,c   Banito, Ana ^a   Roe, Jae Seok ^c   Alonso Curbelo, Direna ^a   Camiolo, Matthew ^d   Tschaharganeh, Darjus F ^a   Huang, Chun Hao ^a,e   Aksoy, Ozlem ^a,b,c   Bolden, Jessica E ^a   Chen, Chi Chao ^a,e   Fennell, Myles ^a   Thapar, Vishal ^a   Chicas, Agustin ^a   Vakoc, Christopher R ^c   Lowe, Scott W ^a,f  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b WATSON SCHOOL OF BIOLOGICAL SCIENCES   (United States)

^c Simons Center for Quantitative Biology   (United States)

^d STONY BROOK UNIVERSITY   (United States)

^e Weill Cornell Medical Center   (United States)

^f HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ACTIN; BONE MORPHOGENETIC PROTEIN 2; CXCL1 CHEMOKINE; DOXYCYCLINE; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 8; INTERSTITIAL COLLAGENASE; PUROMYCIN; STREPTOMYCIN; STROMELYSIN 2; TOLL LIKE RECEPTOR; BRD4 PROTEIN, HUMAN; GUANOSINE TRIPHOSPHATASE; HISTONE; MEMBRANE PROTEIN; NRAS PROTEIN, HUMAN; NUCLEAR PROTEIN; PROTEIN BINDING; TRANSCRIPTION FACTOR;

ARTICLE; BRD4 GENE; CARCINOGENESIS; CELL CULTURE; CELL CYCLE ARREST; CELL VIABILITY; CHROMATIN IMMUNOPRECIPITATION; COLONY FORMATION; GENE; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOSURVEILLANCE; ONCOGENE; PHENOTYPE; RETROVIRUS INFECTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA SEQUENCE; SENESCENCE; TELOMERE HOMEOSTASIS; TUMOR SUPPRESSOR GENE; ANIMAL; BINDING SITE; BIOLOGY; CELL AGING; CELL CYCLE; CELL PROLIFERATION; CHROMATIN ASSEMBLY AND DISASSEMBLY; CLUSTER ANALYSIS; ENHANCER REGION; FIBROBLAST; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; HIGH THROUGHPUT SEQUENCING; LIVER CELL; METABOLISM; MOUSE; NUCLEOTIDE MOTIF; PARACRINE SIGNALING; POSITION WEIGHT MATRIX; PROCEDURES; TUMOR CELL LINE;

ANIMALS; BINDING SITES; CELL AGING; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CHROMATIN ASSEMBLY AND DISASSEMBLY; CHROMATIN IMMUNOPRECIPITATION; CLUSTER ANALYSIS; COMPUTATIONAL BIOLOGY; ENHANCER ELEMENTS, GENETIC; FIBROBLASTS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GTP PHOSPHOHYDROLASES; HEPATOCYTES; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HISTONES; HUMANS; IMMUNOLOGIC SURVEILLANCE; MEMBRANE PROTEINS; MICE; NUCLEAR PROTEINS; NUCLEOTIDE MOTIFS; ONCOGENES; PARACRINE COMMUNICATION; POSITION-SPECIFIC SCORING MATRICES; PROTEIN BINDING; TRANSCRIPTION FACTORS;

EID: 85011977713     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-16-0217     Document Type: Article

References (77)

1. Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell 2007;130:223-33.
2. Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev 2010;24:2463-79.
3. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res 1961;25:585-621.
4. Prieur A, Peeper DS. Cellular senescence in vivo: A barrier to tumori-genesis. Curr Opin Cell Biol 2008;20:150-5.
5. Collado M., Serrano M. Senescence in tumours: Evidence from mice and humans. Nat Rev Cancer 2010;10:51-7.
6. te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 2002; 62: 1876-83.
7. Roninson IB. Tumor cell senescence in cancer treatment. Cancer Res 2003; 63: 2705-15.
8. Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, et al. A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 2002;109:335-46.
9. Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, et al. Senescence of activated stellate cells limits liver fibrosis. Cell 2008;134:657-67.
10. Jun JI, Lau LF. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol 2010;12:676-85.
11. Muñoz-Espín D, Cañamero M, Maraver A, Gómez-López G, Contreras J., Murillo-Cuesta S., et al. Programmed cell senescence during mammalian embryonic development. Cell 2013; 155: 1104-18.
12. Storer M., Mas A, Robert-Moreno A, Pecoraro M., Ortells MC., Di Giacomo V, et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 2013; 155: 1119-30.
13. Demaria M., Ohtani N., Youssef SA., Rodier F, Toussaint W, Mitchell JR, et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell 2014;31:722-33.
14. Muñoz-Espín D., Serrano M. Cellular senescence: From physiology to pathology. Nat Rev Mol Cell Biol 2014; 15: 482-96.
15. Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM., et al. Stem cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 2006;443:421-6.
16. Burd CE., Sorrentino JA, Clark KS., Darr DB., Krishnamurthy J., Deal AM., et al. Monitoring tumorigenesis and senescence in vivo with a p 16(INK4a)-luciferase model. Cell 2013;152:340-51.
17. Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 2016; 530: 184-9.
18. van Deursen JM. The role of senescent cells in ageing. Nature 2014; 509: 439-46.
19. Serrano M., Lin AW, McCurrach ME., Beach D., Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997;88:593-602.
20. Narita M, Nunez S, Heard E, Narita M, Lin AW, Hearn SA, et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 2003; 113: 703-16.
21. Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, et al. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev Cell 2005; 8: 19-30.
22. Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: The dark side of tumor suppression. Annu Rev Pathol 2010;5:99-118.
23. Freund A, Orjalo AV, Desprez PY, Campisi J. Inflammatory networks during cellular senescence: Causes and consequences. Trends Mol Med 2010; 16: 238-46.
24. Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J, et al. Senescence-associated secretory phenotypes reveal cell-nonautono-mous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008; 6: 2853-68.
25. Kuilman T, Peeper DS. Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer 2009; 9: 81-94.
26. Chien Y, Scuoppo C., Wang X., Fang X., Balgley B., Bolden JE, et al. Control of the senescence-associated secretory phenotype by NF-kB promotes senescence and enhances chemosensitivity. Genes Dev 2011;25:2125-36.
27. Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ., et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 2008; 133: 1019-31.
28. Laberge RM., Sun Y, Orjalo AV, Patil CK., Freund A., Zhou L, et al. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol 2015; 17: 1049-61.
29. Herranz N., Gallage S., Mellone M., Wuestefeld T, Klotz S., Hanley CJ. mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype. Nat Cell Biol 2015;17:1205-17.
30. Chen H., Ruiz PD., McKimpson WM., Novikov L., Kitsis RN., Gamble MJ. MacroH2A1 and ATM play opposing roles in paracrine senescence and the senescence-associated secretory phenotype. Mol Cell 2015;59:719-31.
31. Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science 2015; 349: aaa5612.
32. Iannello A., Thompson TW, Ardolino M., Lowe SW, Raulet DH. p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J Exp Med 2013;210:2057-69.
33. Lujambio A, Akkari L., Simon J., Grace D., Tschaharganeh FD., Bolden JE., et al. Non-cell-autonomous tumor suppression by p53. Cell 2013;153:449-60.
34. Sagiv A., Biran A, Yon M., Simon J., Lowe SW, Krizhanovsky V. Granule exocytosis mediates immune surveillance of senescent cells. Oncogene 2013;32:1971-7.
35. Xue W, Zender L., Miething C., Dickins RA, Hernando E., Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445: 656-60.
36. Kang TW, Yevsa T, Woller N, Hoenicke L, Wuestefeld T, Dauch D, et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 2011; 479: 547-51.
37. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, et al. Super-enhancers in the control of cell identity and disease. Cell Resource 2013; 155: 934-47.
38. Whyte WA, Orlando DA., Hnisz D., Abraham BJ., Lin CY, Kagey MH., et al. Master transcription factors and mediator establish superenhancers at key cell identity genes. Cell 2013;153:307-19.
39. Lovén J., Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR., et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 2013; 153: 320-34.
40. Brown JD., Lin CY, Duan Q., Griffin G., Federation AJ., Paranal RM., et al. NF-kB directs dynamic super enhancer formation in inflammation and atherogenesis. Mol Cell 2014;56:219-31.
41. Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, et al. Suppression of inflammation by a synthetic histone mimic. Nature 2010; 468: 1119-23.
42. Filippakopoulos P, Qi J., Picaud S., Shen Y, Smith WB., Fedorov O., et al. Selective Filippakopoulos inhibition of BET bromodomains. Nature 2010;468; 1067-73.
43. Shi J, Vakoc CR The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol Cell 2014;54:728-36.
44. Courtois-Cox S, Jones SL, Cichowski K. Many roads lead to oncogene-induced senescence. Oncogene 2008;27:2801-9.
45. Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ, et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 2010;107:21931-6.
46. Courtois-Cox S, Genther Williams SM, Reczek EE, Johnson BW, McGillicuddy LT, Johannessen CM, et al. A negative feedback signaling network underlies oncogene-induced senescence. Cancer Cell 2006;10:459-72.
47. Olivieri F, Rippo MR, Prattichizzo F, Babini L, Graciotti L, Recchioni R, et al. Toll like receptor signaling in “inflammaging”: microRNA as new players. Immun Ageing 2013;19:11.
48. Shelton DN, Chang E, Whittier PS, Choi D, Funk WD. Microarray analysis of replicative senescence. Curr Biol 1999;9:939-45.
49. Chicas A, Wang X, Zhang C, McCurrach M, Zhao Z, Mert O, et al. Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. Cancer Cell 2010;17:376-87.
50. Gille H, Sharrocks AD, Shaw PE. Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature 1992;358:414-7.
51. Vijayachandra K, Lee J, Glick AB. Smad3 regulates senescence and malignant conversion in a mouse multistage skin carcinogenesis model. Cancer Res 2003;63:3447-52.
52. Acosta JC, O’Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, et al. Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 2008;133:1006-18.
53. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011;478:524-8.
54. Mason DX, Jackson TJ, Lin AW. Molecular signature of oncogenic ras-induced senescence. Oncogene 2004;23:9238-46.
55. Fridman AL, Tainsky MA. Critical pathways in cellular senescence and immortalization revealed by gene expression profiling. Oncogene 2008;27:5975-87.
56. Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 2008;132:363-74.
57. Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, et al. A complex secretory program orchestrated by the inflamma-some controls paracrine senescence. Nat Cell Biol 2013;15:978-90.
58. Belkina AC, Nikolajczyk BS, Denis GV. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses. J Immunol 2013;190:3670-8.
59. Capell BC, Drake AM, Zhu J, Shah PP, Dou Z, Dorsey J, et al. MLL1 is essential for the senescence-associated secretory phenotype. Genes Dev 2016;30:321-36.
60. Shlyueva D, Stampfel G, Stark A. Transcriptional enhancers: From properties to genome-wide predictions. Nat Rev Genet 2014;15:272-86.
61. Ostuni R, Piccolo V, Barozzi I, Polletti S, Termanini A, Bonifacio S, et al. Latent enhancers activated by stimulation in differentiated cells. Cell 2013;152:157-71.
62. Orjalo AV, Bhaumik D, Gengler BK, Scott GK, Campisi J. Cell surface-bound IL-1a is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc Natl Acad Sci U S A 2009;106: 17031-6.
63. Shi J, Wang Y, Zeng L, Wu Y, Deng J, Zhang Q, et al. Disrupting the interaction of BRD4 with diacetylated Twist suppresses tumorigen-esis in basal-like breast cancer. Cancer Cell 2014;25:210-25.
64. Wu T, Pinto HB, Kamikawa YF, Donohoe ME. The BET family member BRD4 interacts with OCT4 and regulates pluripotency gene expression. Stem Cell Reports 2015;4:390-403.
65. Roe JS, Mercan F, Rivera K, Pappin DJ, Vakoc CR BET bromodomain inhibition suppresses the function of hematopoietic transcription factors in acute myeloid leukemia. Mol Cell 2015;58:1028-36.
66. Huang B, Yang XD, Zhou MM, Ozato K, Chen LF. Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acety-lated RelA. Mol Cell Biol 2009;29:1375-87.
67. Ding N, Hah N, Yu RT, Sherman MH, Benner C, Leblanc M, et al. BRD4 is a novel therapeutic target for liver fibrosis. Proc Natl Acad Sci U S A 2015;112:15713-8.
68. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011;146:904-17.
69. Alsarraj J, Walker RC, Webster JD, Geiger TR, Crawford NP, Simpson RM, et al. Deletion of the proline-rich region of the murine metastasis susceptibility gene Brd4 promotes epithelial-to-mesenchymal transition-and stem cell-like conversion. Cancer Res 2011;71:3121-31.
70. Fernandez P, Scaffidi P, Markert E, Lee JH, Rane S, Misteli T. Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4. Cell Rep 2014;9;248-60.
71. Bolden JE, Tasdemir N, Dow LE, van Es JH, Wilkinson JE, Zhao Z, et al. Inducible in vivo silencing of Brd4 identifies potential toxicities of sustained BET protein inhibition. Cell Rep 2014;8:1919-29.
72. Wu SY, Lee AY, Lai HT, Zhang H, Chiang CM. Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting. Mol Cell 2013;49:843-57.
73. Hinkal GW, Gatza CE, Parikh N, Donehower LA. Altered senescence, apoptosis, and DNA damage response in a mutant p53 model of accelerated aging. Mech Dev Ageing 2009;130:262-71.
74. Menck K, Behme D, Pantke M, Reiling N, Binder C, Pukrop T, et al. Isolation of human monocytes by double gradient centrifugation and their differentiation to macrophages in teflon-coated cell culture bags. J Vis Exp 2014;91:e51554.
75. Jaguin M, Houlbert N, Fardel O, Lecureur V. Polarization profiles of human M-CSF-generated macrophages and comparison of M1-mark-ers in classically activated macrophages from GM-CSF and M-CSF origin. Cell Immunol 2013;281:51-61.
76. Joshi AD, Oak SR, Hartigan AJ, Finn WG, Kunkel SL, Duffy KE, et al. Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages. BMC Immunol 2010; 11:52.
77. McLean CY, Bristor D, Hiller M, Clarke SL, Schaar BT, Lowe CB, et al. GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol 2010;28:495-501.