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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},
}