%0 Journal Article
%A Wiese, Maria
%A Walther, Neele
%A Diederichs, Christopher
%A Schill, Fabian
%A Monecke, Sebastian
%A Salinas, Gabriela
%A Sturm, Dominik
%A Pfister, Stefan
%A Dressel, Ralf
%A Johnsen, Steven A
%A Kramm, Christof M
%T The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner.
%J OncoTarget
%V 8
%N 16
%@ 1949-2553
%C [S.l.]
%I Impact Journals LLC
%M DKFZ-2017-01065
%P 27300-27313
%D 2017
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28460484
%2 pmc:PMC5432336
%R 10.18632/oncotarget.15934
%U https://inrepo02.dkfz.de/record/120637