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

Kerosuo, Laura ; Neppala, Pushpa ; Hsin, Jenny ; Mohlin, Sofie LU orcid ; Vieceli, Felipe Monteleone ; Török, Zsofia ; Laine, Anni ; Westermarck, Jukka and Bronner, Marianne E. (2018) In Proceedings of the National Academy of Sciences of the United States of America 115(31). p.7351-7360
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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CIP2A, MycN, Neural crest, Neuroblastoma initiation, Sox2
in
Proceedings of the National Academy of Sciences of the United States of America
volume
115
issue
31
pages
7351 - 7360
publisher
National Academy of Sciences
external identifiers
  • pmid:30021854
  • scopus:85051809828
ISSN
0027-8424
DOI
10.1073/pnas.1800039115
language
English
LU publication?
yes
id
8d017ae7-8b87-4734-b70a-dd5ca61b0ced
date added to LUP
2018-09-11 13:12:35
date last changed
2025-01-08 14:25:08
@article{8d017ae7-8b87-4734-b70a-dd5ca61b0ced,
  abstract     = {{<p>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.</p>}},
  author       = {{Kerosuo, Laura and Neppala, Pushpa and Hsin, Jenny and Mohlin, Sofie and Vieceli, Felipe Monteleone and Török, Zsofia and Laine, Anni and Westermarck, Jukka and Bronner, Marianne E.}},
  issn         = {{0027-8424}},
  keywords     = {{CIP2A; MycN; Neural crest; Neuroblastoma initiation; Sox2}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{31}},
  pages        = {{7351--7360}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate : Implications for priming of neuroblastoma}},
  url          = {{http://dx.doi.org/10.1073/pnas.1800039115}},
  doi          = {{10.1073/pnas.1800039115}},
  volume       = {{115}},
  year         = {{2018}},
}