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@ARTICLE{Wiese:120637,
author = {M. Wiese and N. Walther and C. Diederichs and F. Schill and
S. Monecke and G. Salinas and D. Sturm$^*$ and S.
Pfister$^*$ and R. Dressel and S. A. Johnsen and C. M.
Kramm},
title = {{T}he β-catenin/{CBP}-antagonist {ICG}-001 inhibits
pediatric glioma tumorigenicity in a {W}nt-independent
manner.},
journal = {OncoTarget},
volume = {8},
number = {16},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-01065},
pages = {27300-27313},
year = {2017},
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.},
cin = {B062},
ddc = {610},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28460484},
pmc = {pmc:PMC5432336},
doi = {10.18632/oncotarget.15934},
url = {https://inrepo02.dkfz.de/record/120637},
}