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  • Claeys, ShanaGhent University Hospital,Ghent University (author)

ALK positively regulates MYCN activity through repression of HBP1 expression

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2018-12-11
  • Springer Science and Business Media LLC,2019

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:1d27b9ca-bdd8-4170-857e-850f2eb9c0c4
  • https://lup.lub.lu.se/record/1d27b9ca-bdd8-4170-857e-850f2eb9c0c4URI
  • https://doi.org/10.1038/s41388-018-0595-3DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • ALK mutations occur in 10% of primary neuroblastomas and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype resulting in very poor patient prognosis. To open up opportunities for future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor entity will be essential. We show that mutant ALK downregulates the ‘HMG-box transcription factor 1’ (HBP1) through the PI3K-AKT–FOXO3a signaling axis. HBP1 inhibits both the transcriptional activating and repressing activity of MYCN, the latter being mediated through PRC2 activity. HBP1 itself is under negative control of MYCN through miR-17~92. Combined targeting of HBP1 by PI3K antagonists and MYCN signaling by BET- or HDAC-inhibitors blocks MYCN activity and significantly reduces tumor growth, suggesting a novel targeted therapy option for high-risk neuroblastoma.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Denecker, GeertruiGhent University,Ghent University Hospital (author)
  • Durinck, KaatGhent University Hospital,Ghent University (author)
  • Decaesteker, BiekeGhent University,Ghent University Hospital (author)
  • Mus, Liselot M.Ghent University Hospital,Ghent University (author)
  • Loontiens, SiebeGhent University Hospital,Ghent University (author)
  • Vanhauwaert, SuzanneGhent University,Ghent University Hospital (author)
  • Althoff, KristinaUniversity Hospital Essen (author)
  • Wigerup, CarolineLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)pat-cho (author)
  • Bexell, DanielLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)stem-dbe (author)
  • Dolman, EmmyPrincess Maxima Center for Pediatric Oncology/Hematology (author)
  • Henrich, Kai OliverGerman Cancer Research Centre (author)
  • Wehrmann, LeaGerman Cancer Research Centre (author)
  • Westerhout, Ellen M.Academic Medical Center of University of Amsterdam (AMC) (author)
  • Demoulin, Jean BaptisteCatholic University of Louvain (author)
  • Kumps, CandyGhent University Hospital (author)
  • Van Maerken, TomGhent University Hospital,Ghent University (author)
  • Laureys, GenevieveGhent University,Ghent University Hospital (author)
  • Van Neste, ChristopheGhent University Hospital,Ghent University (author)
  • De Wilde, BramGhent University,Ghent University Hospital (author)
  • De Wever, OlivierGhent University (author)
  • Westermann, FrankGerman Cancer Research Centre (author)
  • Versteeg, RogierAcademic Medical Center of University of Amsterdam (AMC) (author)
  • Molenaar, Jan J.Princess Maxima Center for Pediatric Oncology/Hematology (author)
  • Påhlman, SvenLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)molm-spa (author)
  • Schulte, Johannes H.Charité - University Medicine Berlin (author)
  • De Preter, KatleenGhent University,Ghent University Hospital (author)
  • Speleman, FrankGhent University Hospital,Ghent University (author)
  • Ghent University HospitalGhent University (creator_code:org_t)

Related titles

  • In:Oncogene: Springer Science and Business Media LLC38:15, s. 2690-27050950-92321476-5594

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