Wiese, Maria

[["dc.bibliographiccitation.firstpage","27300"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","27313"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Wiese, Maria"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Diederichs, Christopher"],["dc.contributor.author","Schill, Fabian"],["dc.contributor.author","Monecke, Sebastian"],["dc.contributor.author","Salinas, Gabriella"],["dc.contributor.author","Sturm, Dominik"],["dc.contributor.author","Pfister, Stefan"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Johnsen, Steven Arthur"],["dc.contributor.author","Kramm, Christof M."],["dc.date.accessioned","2018-10-10T07:29:11Z"],["dc.date.available","2018-10-10T07:29:11Z"],["dc.date.issued","2017-04-18"],["dc.description.abstract","Pediatric high-grade gliomas (pedHGG) belong to the most aggressive cancers in children with a poor prognosis due to a lack of efficient therapeutic strategies. The β-catenin/Wnt-signaling pathway was shown to hold promising potential as a treatment target in adult high-grade gliomas by abrogating tumor cell invasion and the acquisition of stem cell-like characteristics. Since pedHGG differ from their adult counterparts in genetically and biologically we aimed to investigate the effects of β-catenin/Wnt-signaling pathway-inhibition by the β-catenin/CBP antagonist ICG-001 in pedHGG cell lines. In contrast to adult HGG, pedHGG cells displayed minimal detectable canonical Wnt-signaling activity. Nevertheless, low doses of ICG-001 inhibited cell migration/invasion, tumorsphere- and colony formation, proliferation in vitro as well as tumor growth in vivo/ovo, suggesting that ICG-001 affects pedHGG tumor cell characteristics independent of β-catenin/Wnt-signaling. RNA-sequencing analyses support a Wnt/β-catenin-independent effect of ICG-001 on target gene transcription, revealing strong effects on genes involved in cellular metabolic/biosynthetic processes and cell cycle progression. Among these, high mRNA expression of cell cycle regulator JDP2 was found to confer a better prognosis for pedHGG patients. In conclusion, ICG-001 might offer an effective treatment option for pedHGG patients functioning to regulate cell phenotype and gene expression programs in absence of Wnt/β-catenin signaling-activity."],["dc.fs.pkfprnr","86261"],["dc.identifier.doi","10.18632/oncotarget.15934"],["dc.identifier.fs","633047"],["dc.identifier.pmid","28460484"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14424"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15920"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]