BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway Journal Article
| Authors: | Green, A. L.; DeSisto, J.; Flannery, P.; Lemma, R.; Knox, A.; Lemieux, M.; Sanford, B.; O’Rourke, R.; Ramkissoon, S.; Jones, K.; Perry, J.; Hui, X.; Moroze, E.; Balakrishnan, I.; O’Neill, A. F.; Dunn, K.; DeRyckere, D.; Danis, E.; Safadi, A.; Gilani, A.; Hubbell-Engler, B.; Nuss, Z.; Levy, J. M. M.; Serkova, N.; Venkataraman, S.; Graham, D. K.; Foreman, N.; Ligon, K.; Jones, K.; Kung, A. L.; Vibhakar, R. |
| Article Title: | BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway |
| Abstract: | 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, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | signal transduction; adult; child; controlled study; human cell; clinical feature; cancer growth; nonhuman; glioma; cancer grading; cell proliferation; mouse; animal tissue; gene overexpression; animal experiment; animal model; in vivo study; neural stem cell; in vitro study; carcinogenesis; gene expression regulation; cancer inhibition; oncogene; chromatin; myc protein; gene repression; oncogene myc; cell self-renewal; gene knockdown; human; female; priority journal; article; epigenetic repression; glioblastoma cell line; bptf gene |
| Journal Title: | Oncogene |
| Volume: | 39 |
| Issue: | 11 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-03-12 |
| Start Page: | 2305 |
| End Page: | 2327 |
| Language: | English |
| DOI: | 10.1038/s41388-019-1125-7 |
| PUBMED: | 31844250 |
| PROVIDER: | scopus |
| PMCID: | PMC7071968 |
| DOI/URL: | |
| Notes: | Article -- Erratum issued, see DOI: 10.1038/s41388-020-1155-1 -- Export Date: 1 April 2020 -- Source: Scopus |
