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

Maria Wiese, Neele Walther, Christopher Diederichs, Fabian Schill, Sebastian Monecke, Gabriela Salinas, Dominik Sturm, Stefan M. Pfister, Ralf Dressel, Steven Johnsen, Christof M. Kramm

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)27300-27313
Number of pages14
JournalOncotarget
Volume8
Issue number16
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Catenins
Glioma
Pediatrics
Wnt Signaling Pathway
Neoplasms
Cell Cycle
RNA Sequence Analysis
ICG 001
Genes
Cell Movement
Stem Cells
Therapeutics
Phenotype
Gene Expression
Cell Line
Messenger RNA
Growth

Keywords

  • Cell cycle
  • CREB binding protein (CBP)
  • ICG-001
  • Pediatric high-grade glioma (pedHGG)
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Oncology

Cite this

Wiese, M., Walther, N., Diederichs, C., Schill, F., Monecke, S., Salinas, G., ... Kramm, C. M. (2017). The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner. Oncotarget, 8(16), 27300-27313. https://doi.org/10.18632/oncotarget.15934

The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner. / Wiese, Maria; Walther, Neele; Diederichs, Christopher; Schill, Fabian; Monecke, Sebastian; Salinas, Gabriela; Sturm, Dominik; Pfister, Stefan M.; Dressel, Ralf; Johnsen, Steven; Kramm, Christof M.

In: Oncotarget, Vol. 8, No. 16, 01.01.2017, p. 27300-27313.

Research output: Contribution to journalArticle

Wiese, M, Walther, N, Diederichs, C, Schill, F, Monecke, S, Salinas, G, Sturm, D, Pfister, SM, Dressel, R, Johnsen, S & Kramm, CM 2017, 'The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner', Oncotarget, vol. 8, no. 16, pp. 27300-27313. https://doi.org/10.18632/oncotarget.15934
Wiese M, Walther N, Diederichs C, Schill F, Monecke S, Salinas G et al. The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner. Oncotarget. 2017 Jan 1;8(16):27300-27313. https://doi.org/10.18632/oncotarget.15934
Wiese, Maria ; Walther, Neele ; Diederichs, Christopher ; Schill, Fabian ; Monecke, Sebastian ; Salinas, Gabriela ; Sturm, Dominik ; Pfister, Stefan M. ; Dressel, Ralf ; Johnsen, Steven ; Kramm, Christof M. / The β-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner. In: Oncotarget. 2017 ; Vol. 8, No. 16. pp. 27300-27313.
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