Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma

Research output: Contribution to journalArticle

Abstract

Neuroblastoma is a neural crest-derived childhood tumor of the peripheral nervous system in which MycN amplification is a hallmark of poor prognosis. Here we show that MycN is expressed together with phosphorylation-stabilizing factor CIP2A in regions of the neural plate destined to form the CNS, but MycN is excluded from the neighboring neural crest stem cell domain. Interestingly, ectopic expression of MycN or CIP2A in the neural crest domain biases cells toward CNS-like neural stem cells that express Sox2. Consistent with this, some forms of neuroblastoma have been shown to share transcriptional resemblance with CNS neural stem cells. As high MycN/CIP2A levels correlate with poor prognosis, we posit that a MycN/CIP2A-mediated cell-fate bias may reflect a possible mechanism underlying early priming of some aggressive forms of neuroblastoma. In contrast to MycN, its paralogue cMyc is normally expressed in the neural crest stem cell domain and typically is associated with better overall survival in clinical neuroblastoma, perhaps reflecting a more “normal” neural crest-like state. These data suggest that priming for some forms of aggressive neuroblastoma may occur before neural crest emigration from the CNS and well before sympathoadrenal specification.

Details

Authors
  • Laura Kerosuo
  • Pushpa Neppala
  • Jenny Hsin
  • Sofie Mohlin
  • Felipe Monteleone Vieceli
  • Zsofia Török
  • Anni Laine
  • Jukka Westermarck
  • Marianne E. Bronner
Organisations
External organisations
  • California Institute of Technology
  • University of Turku
  • Åbo Akademi University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • CIP2A, MycN, Neural crest, Neuroblastoma initiation, Sox2
Original languageEnglish
Pages (from-to)E7351-E7360
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number31
Publication statusPublished - 2018 Jul 31
Publication categoryResearch
Peer-reviewedYes