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The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner

ABSTRACT: In pediatric glioma cell lines, treatment with ICG-001 had no inhibitory effect on canonical Wnt-target genes but induced significant up regulation of various known β-catenin target genes in both cell lines and top 20 GO-annotations of down-regulated genes by ICG-001 were associated with biosynthetic and metabolic processes and cell cycle division processes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE83266 | GEO | 2016/06/14

SECONDARY ACCESSION(S): PRJNA325456

REPOSITORIES: GEO

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The Î²-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner

Project description:In pediatric glioma cell lines, treatment with ICG-001 had no inhibitory effect on canonical Wnt-target genes but induced significant up regulation of various known Î²-catenin target genes in both cell lines and top 20 GO-annotations of down-regulated genes by ICG-001 were associated with biosynthetic and metabolic processes and cell cycle division processes. Pediatric cell lines were treated with ICG-001 or DMSO for 48h

2016-06-14 | E-GEOD-83266 | biostudies-arrayexpress

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ICG-001 activates a series of ER stress response genes in monocyte derived macrophages (MDMs)

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Project description:This study aims to characterize gene expression changes upon treatment with JQ1, ICG-001, and combined treatment. The general goal is to identify the mechanism for high efficacy of combinatorial treatment of BET and CBP inhibition in DIPG cells.

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The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner.

Project description: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.

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