BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
02
10
2018
accepted:
20
11
2019
revised:
15
11
2019
pubmed:
18
12
2019
medline:
18
12
2019
entrez:
18
12
2019
Statut:
ppublish
Résumé
High-grade gliomas (HGG) afflict both children and adults and respond poorly to current therapies. Epigenetic regulators have a role in gliomagenesis, but a broad, functional investigation of the impact and role of specific epigenetic targets has not been undertaken. Using a two-step, in vitro/in vivo epigenomic shRNA inhibition screen, we determine the chromatin remodeler BPTF to be a key regulator of adult HGG growth. We then demonstrate that BPTF knockdown decreases HGG growth in multiple pediatric HGG models as well. BPTF appears to regulate tumor growth through cell self-renewal maintenance, and BPTF knockdown leads these glial tumors toward more neuronal characteristics. BPTF's impact on growth is mediated through positive effects on expression of MYC and MYC pathway targets. HDAC inhibitors synergize with BPTF knockdown against HGG growth. BPTF inhibition is a promising strategy to combat HGG through epigenetic regulation of the MYC oncogenic pathway.
Identifiants
pubmed: 31844250
doi: 10.1038/s41388-019-1125-7
pii: 10.1038/s41388-019-1125-7
pmc: PMC7071968
mid: NIHMS1544187
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2305-2327Subventions
Organisme : NINDS NIH HHS
ID : L40 NS098453
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS048154
Pays : United States
Organisme : NIH HHS
ID : S10 OD023485
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD068372
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS086839
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046934
Pays : United States
Commentaires et corrections
Type : ErratumIn
Références
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathologica. 2007;114:97–109.
pubmed: 17618441
pmcid: 1929165
Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008;359:492–507. (Research support, N.I.H., extramural research support, Non-U.S. Gov’t Review).
pubmed: 18669428
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.
pubmed: 15758009
pmcid: 15758009
Fangusaro J. Pediatric high-grade gliomas and diffuse intrinsic pontine gliomas. J Child Neurol. 2009;24:1409–17.
pubmed: 19638636
Rodriguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med. 2011;17:330–9.
pubmed: 21386836
Clarke J, Penas C, Pastori C, Komotar RJ, Bregy A, Shah AH, et al. Epigenetic pathways and glioblastoma treatment. Epigenetics. 2013;8:785–95.
pubmed: 23807265
pmcid: 3883781
Maleszewska M, Kaminska B. Is glioblastoma an epigenetic malignancy? Cancers. 2013;5:1120–39.
pubmed: 24202337
pmcid: 3795382
Ferreira WA, Pinheiro Ddo R, Costa Junior CA, Rodrigues-Antunes S, Araujo MD, Leao Barros MB, et al. An update on the epigenetics of glioblastomas. Epigenomics. 2016;8:1289–305.
pubmed: 27585647
Touat M, Idbaih A, Sanson M, Ligon KL. Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann Oncol. 2017;28:1457–72.
pubmed: 28863449
pmcid: 5834086
Lulla RR, Saratsis AM, Hashizume R. Mutations in chromatin machinery and pediatric high-grade glioma. Sci Adv. 2016;2:e1501354.
pubmed: 27034984
pmcid: 4803494
Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012;482:226–31.
pubmed: 22286061
Ghantous A, Hernandez-Vargas H, Byrnes G, Dwyer T, Herceg Z. Characterising the epigenome as a key component of the fetal exposome in evaluating in utero exposures and childhood cancer risk. Mutagenesis. 2015;30:733–42.
pubmed: 25724893
pmcid: 4757935
Miozzo M, Vaira V, Sirchia SM. Epigenetic alterations in cancer and personalized cancer treatment. Future Oncol. 2015;11:333–48.
pubmed: 25591842
Lee P, Murphy B, Miller R, Menon V, Banik NL, Giglio P, et al. Mechanisms and clinical significance of histone deacetylase inhibitors: epigenetic glioblastoma therapy. Anticancer Res. 2015;35:615–25.
pubmed: 25667438
pmcid: 6052863
Morales La Madrid A, Hashizume R, Kieran MW. Future clinical trials in DIPG: bringing epigenetics to the clinic. Front Oncol. 2015;5:148.
pubmed: 26191506
pmcid: 4486770
Mottamal M, Zheng S, Huang TL, Wang G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules. 2015;20:3898–941.
pubmed: 25738536
pmcid: 25738536
Herms JW, von Loewenich FD, Behnke J, Markakis E, Kretzschmar HA. c-myc oncogene family expression in glioblastoma and survival. Surg Neurol. 1999;51:536–42.
pubmed: 10321885
Wang J, Wang H, Li Z, Wu Q, Lathia JD, McLendon RE, et al. c-Myc is required for maintenance of glioma cancer stem cells. PloS ONE. 2008;3:e3769.
pubmed: 19020659
pmcid: 2582454
Broad D DepMap Achilles 19Q1 Public. Broad Institute, Cambridge, MA, 2019.
Ghandi M, Huang FW, Jané-Valbuena J, Kryukov GV, Lo CC, McDonald ER, et al. Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019;569:503–8.
pubmed: 31068700
pmcid: 6697103
Meyers RM, Bryan JG, McFarland JM, Weir BA, Sizemore AE, Xu H, et al. Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells. Nat Genet. 2017;49:1779–84.
pubmed: 29083409
pmcid: 5709193
Xie Q, Wu QL, Kim L, Miller TE, Liau BB, Mack SC, et al. RBPJ maintains brain tumor-initiating cells through CDK9-mediated transcriptional elongation. J Clin Investig. 2016;126:2757–72.
pubmed: 27322055
Bao SD, Wu QL, McLendon RE, Hao YL, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–60.
pubmed: 17051156
Urick AK, Hawk LM, Cassel MK, Mishra NK, Liu S, Adhikari N, et al. Dual screening of BPTF and Brd4 using protein-observed fluorine NMR uncovers new bromodomain probe molecules. ACS Chem Biol. 2015;10:2246–56.
pubmed: 26158404
pmcid: 4858447
Li H, Ilin S, Wang W, Duncan EM, Wysocka J, Allis CD, et al. Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF. Nature. 2006;442:91–5.
pubmed: 16728978
pmcid: 4690523
Stankiewicz P, Khan TN, Szafranski P, Slattery L, Streff H, Vetrini F, et al. Haploinsufficiency of the chromatin remodeler BPTF causes syndromic developmental and speech delay, postnatal microcephaly, and dysmorphic features. Am J Hum Genet. 2017;101:503–15.
pubmed: 28942966
pmcid: 5630163
Bekpen C, Tastekin I, Siswara P, Akdis CA, Eichler EE. Primate segmental duplication creates novel promoters for the LRRC37 gene family within the 17q21.31 inversion polymorphism region. Genome Res. 2012;22:1050–8.
pubmed: 22419166
pmcid: 3371713
Ma Y, Liu X, Liu Z, Wei S, Shang H, Xue Y, et al. The chromatin remodeling protein Bptf promotes posterior neuroectodermal fate by enhancing Smad2-activated wnt8a expression. J Neurosci. 2015;35:8493–506.
pubmed: 26041917
pmcid: 6605332
Gong YC, Liu DC, Li XP, Dai SP. BPTF biomarker correlates with poor survival in human NSCLC. Eur Rev Med Pharm Sci. 2017;21:102–7.
Buganim Y, Goldstein I, Lipson D, Milyavsky M, Polak-Charcon S, Mardoukh C, et al. A novel translocation breakpoint within the BPTF gene is associated with a pre-malignant phenotype. PloS ONE. 2010;5:e9657.
pubmed: 20300178
pmcid: 2836376
Lee JH, Kim MS, Yoo NJ, Lee SH. BPTF, a chromatin remodeling-related gene, exhibits frameshift mutations in gastric and colorectal cancers. APMIS. 2016;124:425–7.
pubmed: 26899553
Xiao S, Liu L, Fang M, Zhou X, Peng X, Long J, et al. BPTF associated with EMT indicates negative prognosis in patients with hepatocellular carcinoma. Dig Dis Sci. 2015;60:910–8.
pubmed: 25362514
Richart L, Carrillo-de Santa Pau E, Rio-Machin A, de Andres MP, Cigudosa JC, Lobo VJ, et al. BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis. Nat Commun. 2016;7:10153.
pubmed: 26729287
pmcid: 4728380
Dai M, Lu JJ, Guo W, Yu W, Wang Q, Tang R, et al. BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas. Oncotarget. 2015;6:33878–92.
pubmed: 26418899
pmcid: 4741809
Dar AA, Nosrati M, Bezrookove V, de Semir D, Majid S, Thummala S, et al. The role of BPTF in melanoma progression and in response to BRAF-targeted therapy. J Natl Cancer Inst. 2015;107:pii:djv034.
Xiao S, Liu L, Lu X, Long J, Zhou X, Fang M. The prognostic significance of bromodomain PHD-finger transcription factor in colorectal carcinoma and association with vimentin and E-cadherin. J Cancer Res Clin Oncol. 2015;141:1465–74.
pubmed: 25716692
Frey WD, Chaudhry A, Slepicka PF, Ouellette AM, Kirberger SE, Pomerantz WCK, et al. BPTF maintains chromatin accessibility and the self-renewal capacity of mammary gland stem cells. Stem Cell Rep. 2017;9:23–31.
Kim J, Lo L, Dormand E, Anderson DJ. SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells. Neuron. 2003;38:17–31.
pubmed: 12691661
Bramanti V, Tomassoni D, Avitabile M, Amenta F, Avola R. Biomarkers of glial cell proliferation and differentiation in culture. Front Biosci. 2010;2:558–70.
Person F, Wilczak W, Hube-Magg C, Burdelski C, Moller-Koop C, Simon R, et al. Prevalence of betaIII-tubulin (TUBB3) expression in human normal tissues and cancers. Tumour Biol. 2017;39:1010428317712166.
pubmed: 29022485
Su Z, Niu W, Liu ML, Zou Y, Zhang CL. In vivo conversion of astrocytes to neurons in the injured adult spinal cord. Nat Commun. 2014;5:3338.
pubmed: 24569435
pmcid: 3966078
Bouchard C, Thieke K, Maier A, Saffrich R, Hanley-Hyde J, Ansorge W, et al. Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27. EMBO J. 1999;18:5321–33.
pubmed: 10508165
pmcid: 1171602
Kerosuo L, Piltti K, Fox H, Angers-Loustau A, Hayry V, Eilers M, et al. Myc increases self-renewal in neural progenitor cells through Miz-1. J Cell Sci. 2008;121:3941–50.
pubmed: 19001505
Nebbioso A, Carafa V, Conte M, Tambaro FP, Abbondanza C, Martens J, et al. c-Myc modulation and acetylation is a key HDAC inhibitor target in cancer. Clin Cancer Res. 2017;23:2542–55.
pubmed: 27358484
Grasso CS, Tang Y, Truffaux N, Berlow NE, Liu L, Debily MA, et al. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med. 2015;21:827.
pubmed: 26151328
Lapin DH, Tsoli M, Ziegler DS. Genomic insights into diffuse intrinsic pontine glioma. Front Oncol. 2017;7:57.
pubmed: 28401062
pmcid: 5368268
Landry J, Sharov AA, Piao Y, Sharova LV, Xiao H, Southon E, et al. Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells. PLoS Genet. 2008;4:e1000241.
pubmed: 18974875
pmcid: 2570622
Green AL, Ramkissoon SH, McCauley D, Jones K, Perry JA, Hsu JH, et al. Preclinical antitumor efficacy of selective exportin 1 inhibitors in glioblastoma. Neuro Oncol. 2015;17:697–707.
pubmed: 25366336
Baird NL, Bowlin JL, Cohrs RJ, Gilden D, Jones KL. Comparison of varicella-zoster virus RNA sequences in human neurons and fibroblasts. J Virol. 2014;88:5877–80.
pubmed: 24600007
pmcid: 4019124
Wu TD, Nacu S. Fast and SNP-tolerant detection of complex variants and splicing in short reads. Bioinformatics. 2010;26:873–81.
pubmed: 20147302
pmcid: 2844994
Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010;28:511–5.
pubmed: 20436464
pmcid: 3146043
Arrigoni L, Richter AS, Betancourt E, Bruder K, Diehl S, Manke T, et al. Standardizing chromatin research: a simple and universal method for ChIP-seq. Nucleic acids Res. 2016;44:e67.
pubmed: 26704968
Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114–20.
pubmed: 24695404
pmcid: 24695404
Wu TD, Watanabe CK. GMAP: a genomic mapping and alignment program for mRNA and EST sequences. Bioinformatics. 2005;21:1859–75.
pubmed: 15728110
pmcid: 15728110
Ramirez F, Ryan DP, Gruning B, Bhardwaj V, Kilpert F, Richter AS, et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016;44:W160–5.
pubmed: 27079975
pmcid: 4987876
Ross-Innes CS, Stark R, Teschendorff AE, Holmes KA, Ali HR, Dunning MJ, et al. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature. 2012;481:389–93.
pubmed: 22217937
pmcid: 3272464
Benjamini Y, Hochberg YJ. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995;B57:289–300.
Andrade JM, Estevez-Perez MG. Statistical comparison of the slopes of two regression lines: a tutorial. Anal Chim Acta. 2014;838:1–12.
pubmed: 25064237