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BPTF Regulates Growth of Adult and Pediatric High-Grade Glioma through the MYC Pathway

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 vi...

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Autores principales: Green, Adam L., DeSisto, John, Flannery, Patrick, Lemma, Rakeb, Knox, Aaron, Lemieux, Madeleine, Sanford, Bridget, O’Rourke, Rebecca, Ramkissoon, Shakti, Jones, Kristen, Perry, Jennifer, Hui, Xu, Moroze, Erin, Balakrishnan, Ilango, O’Neill, Allison F., Dunn, Katherine, DeRyckere, Deborah, Danis, Etienne, Safadi, Aaron, Gilani, Ahmed, Hubbell-Engler, Benjamin, Nuss, Zachary, Mulcahy Levy, Jean M., Serkova, Natalie, Venkataraman, Sujatha, Graham, Douglas K., Foreman, Nicholas, Ligon, Keith, Jones, Ken, Kung, Andrew, Vibhakar, Rajeev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071968/
https://www.ncbi.nlm.nih.gov/pubmed/31844250
http://dx.doi.org/10.1038/s41388-019-1125-7
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author Green, Adam L.
DeSisto, John
Flannery, Patrick
Lemma, Rakeb
Knox, Aaron
Lemieux, Madeleine
Sanford, Bridget
O’Rourke, Rebecca
Ramkissoon, Shakti
Jones, Kristen
Perry, Jennifer
Hui, Xu
Moroze, Erin
Balakrishnan, Ilango
O’Neill, Allison F.
Dunn, Katherine
DeRyckere, Deborah
Danis, Etienne
Safadi, Aaron
Gilani, Ahmed
Hubbell-Engler, Benjamin
Nuss, Zachary
Mulcahy Levy, Jean M.
Serkova, Natalie
Venkataraman, Sujatha
Graham, Douglas K.
Foreman, Nicholas
Ligon, Keith
Jones, Ken
Kung, Andrew
Vibhakar, Rajeev
author_facet Green, Adam L.
DeSisto, John
Flannery, Patrick
Lemma, Rakeb
Knox, Aaron
Lemieux, Madeleine
Sanford, Bridget
O’Rourke, Rebecca
Ramkissoon, Shakti
Jones, Kristen
Perry, Jennifer
Hui, Xu
Moroze, Erin
Balakrishnan, Ilango
O’Neill, Allison F.
Dunn, Katherine
DeRyckere, Deborah
Danis, Etienne
Safadi, Aaron
Gilani, Ahmed
Hubbell-Engler, Benjamin
Nuss, Zachary
Mulcahy Levy, Jean M.
Serkova, Natalie
Venkataraman, Sujatha
Graham, Douglas K.
Foreman, Nicholas
Ligon, Keith
Jones, Ken
Kung, Andrew
Vibhakar, Rajeev
author_sort Green, Adam L.
collection PubMed
description 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.
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spelling pubmed-70719682020-06-16 BPTF Regulates Growth of Adult and Pediatric High-Grade Glioma through the MYC Pathway Green, Adam L. DeSisto, John Flannery, Patrick Lemma, Rakeb Knox, Aaron Lemieux, Madeleine Sanford, Bridget O’Rourke, Rebecca Ramkissoon, Shakti Jones, Kristen Perry, Jennifer Hui, Xu Moroze, Erin Balakrishnan, Ilango O’Neill, Allison F. Dunn, Katherine DeRyckere, Deborah Danis, Etienne Safadi, Aaron Gilani, Ahmed Hubbell-Engler, Benjamin Nuss, Zachary Mulcahy Levy, Jean M. Serkova, Natalie Venkataraman, Sujatha Graham, Douglas K. Foreman, Nicholas Ligon, Keith Jones, Ken Kung, Andrew Vibhakar, Rajeev Oncogene Article 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. 2019-12-16 2020-03 /pmc/articles/PMC7071968/ /pubmed/31844250 http://dx.doi.org/10.1038/s41388-019-1125-7 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Green, Adam L.
DeSisto, John
Flannery, Patrick
Lemma, Rakeb
Knox, Aaron
Lemieux, Madeleine
Sanford, Bridget
O’Rourke, Rebecca
Ramkissoon, Shakti
Jones, Kristen
Perry, Jennifer
Hui, Xu
Moroze, Erin
Balakrishnan, Ilango
O’Neill, Allison F.
Dunn, Katherine
DeRyckere, Deborah
Danis, Etienne
Safadi, Aaron
Gilani, Ahmed
Hubbell-Engler, Benjamin
Nuss, Zachary
Mulcahy Levy, Jean M.
Serkova, Natalie
Venkataraman, Sujatha
Graham, Douglas K.
Foreman, Nicholas
Ligon, Keith
Jones, Ken
Kung, Andrew
Vibhakar, Rajeev
BPTF Regulates Growth of Adult and Pediatric High-Grade Glioma through the MYC Pathway
title BPTF Regulates Growth of Adult and Pediatric High-Grade Glioma through the MYC Pathway
title_full BPTF Regulates Growth of Adult and Pediatric High-Grade Glioma through the MYC Pathway
title_fullStr BPTF Regulates Growth of Adult and Pediatric High-Grade Glioma through the MYC Pathway
title_full_unstemmed BPTF Regulates Growth of Adult and Pediatric High-Grade Glioma through the MYC Pathway
title_short BPTF Regulates Growth of Adult and Pediatric High-Grade Glioma through the MYC Pathway
title_sort bptf regulates growth of adult and pediatric high-grade glioma through the myc pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071968/
https://www.ncbi.nlm.nih.gov/pubmed/31844250
http://dx.doi.org/10.1038/s41388-019-1125-7
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