Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma
Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the EfnA5 l...
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| Veröffentlicht in: | Oncogene 2020-03, Vol.39 (12), p.2523-2538 |
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| creator | Ricci, Barbara Millner, Thomas O. Pomella, Nicola Zhang, Xinyu Guglielmi, Loredana Badodi, Sara Ceric, Dario Gemma, Carolina Cognolato, Erica Zhang, Ying Brandner, Sebastian Barnes, Michael R. Marino, Silvia |
| description | Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the
EfnA5
locus and reinforces repression of selected target genes in a cellular context-dependent fashion. EfnA5 mediates Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide pre-clinical evidence of druggability of the EFNA5 signalling pathway in GBM xenografts overexpressing Bmi1. |
| doi_str_mv | 10.1038/s41388-020-1161-3 |
| format | Article |
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EfnA5
locus and reinforces repression of selected target genes in a cellular context-dependent fashion. EfnA5 mediates Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide pre-clinical evidence of druggability of the EFNA5 signalling pathway in GBM xenografts overexpressing Bmi1.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/s41388-020-1161-3</identifier><identifier>PMID: 31988455</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/106 ; 13/51 ; 38 ; 38/91 ; 59/5 ; 631/67/70 ; 631/80/304 ; 64/60 ; 96/100 ; 96/63 ; Adults ; Animals ; Antihypertensive Agents - pharmacology ; Apoptosis ; Brain cancer ; Brain tumors ; Care and treatment ; Cell Biology ; Cell cycle ; Cell Proliferation ; Cellular signal transduction ; Dentistry ; Development and progression ; Doxazosin - pharmacology ; Drug Delivery Systems ; Ephrin-A5 - antagonists & inhibitors ; Ephrin-A5 - metabolism ; Ephrins ; Epigenesis, Genetic ; Epigenetics ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene silencing ; Genes ; Genetic aspects ; Genomes ; Glioblastoma ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Glioblastoma multiforme ; Health aspects ; Histones - metabolism ; Human Genetics ; Humans ; Internal Medicine ; Lysine - metabolism ; Medicine ; Medicine & Public Health ; Mice ; Mice, Transgenic ; Mutation ; Neoplasm Invasiveness ; Neural Stem Cells - metabolism ; Neurogenesis ; Oncology ; Physiology ; Polycomb group proteins ; Polycomb Repressive Complex 1 - genetics ; Polycomb Repressive Complex 1 - metabolism ; Signal transduction ; Stem cells ; Tumor Cells, Cultured ; Tumors ; Xenografts</subject><ispartof>Oncogene, 2020-03, Vol.39 (12), p.2523-2538</ispartof><rights>The Author(s) 2020</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c565t-9f7fd1e8e8a75a8425bd173973b4e473759e271960bb7a64b93d2e91ac735fc23</citedby><cites>FETCH-LOGICAL-c565t-9f7fd1e8e8a75a8425bd173973b4e473759e271960bb7a64b93d2e91ac735fc23</cites><orcidid>0000-0002-9821-0342 ; 0000-0002-4890-9972 ; 0000-0002-8407-8336</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31988455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ricci, Barbara</creatorcontrib><creatorcontrib>Millner, Thomas O.</creatorcontrib><creatorcontrib>Pomella, Nicola</creatorcontrib><creatorcontrib>Zhang, Xinyu</creatorcontrib><creatorcontrib>Guglielmi, Loredana</creatorcontrib><creatorcontrib>Badodi, Sara</creatorcontrib><creatorcontrib>Ceric, Dario</creatorcontrib><creatorcontrib>Gemma, Carolina</creatorcontrib><creatorcontrib>Cognolato, Erica</creatorcontrib><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Brandner, Sebastian</creatorcontrib><creatorcontrib>Barnes, Michael R.</creatorcontrib><creatorcontrib>Marino, Silvia</creatorcontrib><title>Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the
EfnA5
locus and reinforces repression of selected target genes in a cellular context-dependent fashion. EfnA5 mediates Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ricci, Barbara</au><au>Millner, Thomas O.</au><au>Pomella, Nicola</au><au>Zhang, Xinyu</au><au>Guglielmi, Loredana</au><au>Badodi, Sara</au><au>Ceric, Dario</au><au>Gemma, Carolina</au><au>Cognolato, Erica</au><au>Zhang, Ying</au><au>Brandner, Sebastian</au><au>Barnes, Michael R.</au><au>Marino, Silvia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>39</volume><issue>12</issue><spage>2523</spage><epage>2538</epage><pages>2523-2538</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><abstract>Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the
EfnA5
locus and reinforces repression of selected target genes in a cellular context-dependent fashion. EfnA5 mediates Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide pre-clinical evidence of druggability of the EFNA5 signalling pathway in GBM xenografts overexpressing Bmi1.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31988455</pmid><doi>10.1038/s41388-020-1161-3</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-9821-0342</orcidid><orcidid>https://orcid.org/0000-0002-4890-9972</orcidid><orcidid>https://orcid.org/0000-0002-8407-8336</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13 13/106 13/51 38 38/91 59/5 631/67/70 631/80/304 64/60 96/100 96/63 Adults Animals Antihypertensive Agents - pharmacology Apoptosis Brain cancer Brain tumors Care and treatment Cell Biology Cell cycle Cell Proliferation Cellular signal transduction Dentistry Development and progression Doxazosin - pharmacology Drug Delivery Systems Ephrin-A5 - antagonists & inhibitors Ephrin-A5 - metabolism Ephrins Epigenesis, Genetic Epigenetics Gene expression Gene Expression Regulation, Neoplastic Gene silencing Genes Genetic aspects Genomes Glioblastoma Glioblastoma - metabolism Glioblastoma - pathology Glioblastoma multiforme Health aspects Histones - metabolism Human Genetics Humans Internal Medicine Lysine - metabolism Medicine Medicine & Public Health Mice Mice, Transgenic Mutation Neoplasm Invasiveness Neural Stem Cells - metabolism Neurogenesis Oncology Physiology Polycomb group proteins Polycomb Repressive Complex 1 - genetics Polycomb Repressive Complex 1 - metabolism Signal transduction Stem cells Tumor Cells, Cultured Tumors Xenografts |
| title | Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma |
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