TY  - JOUR
AU  - Wiese, Maria
AU  - Walther, Neele
AU  - Diederichs, Christopher
AU  - Schill, Fabian
AU  - Monecke, Sebastian
AU  - Salinas, Gabriela
AU  - Sturm, Dominik
AU  - Pfister, Stefan
AU  - Dressel, Ralf
AU  - Johnsen, Steven A
AU  - Kramm, Christof M
TI  - The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner.
JO  - OncoTarget
VL  - 8
IS  - 16
SN  - 1949-2553
CY  - [S.l.]
PB  - Impact Journals LLC
M1  - DKFZ-2017-01065
SP  - 27300-27313
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28460484
C2  - pmc:PMC5432336
DO  - DOI:10.18632/oncotarget.15934
UR  - https://inrepo02.dkfz.de/record/120637
ER  -