guest ::
| Home > Publications database > The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner. |
| Home > Publications database > The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner. |
| Journal Article | DKFZ-2017-01065 |
; ; ; ; ; ; ; ; ; ;
2017
Impact Journals LLC
[S.l.]
This record in other databases: 
Please use a persistent id in citations: doi:10.18632/oncotarget.15934
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.
; BIOSIS Previews ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
|
The record appears in these collections: |
