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

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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; Vieceli, Felipe Monteleone; Török, Zsofia; Laine, Anni; Westermarck, Jukka; Bronner, Marianne E.

I: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, Nr. 31, 31.07.2018, s. E7351-E7360.

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Kerosuo, Laura ; Neppala, Pushpa ; Hsin, Jenny ; Mohlin, Sofie ; Vieceli, Felipe Monteleone ; Török, Zsofia ; Laine, Anni ; Westermarck, Jukka ; Bronner, Marianne E. / Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate : Implications for priming of neuroblastoma. I: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, Nr. 31. s. E7351-E7360.

RIS

TY - JOUR

T1 - Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate

T2 - Proceedings of the National Academy of Sciences

AU - Kerosuo, Laura

AU - Neppala, Pushpa

AU - Hsin, Jenny

AU - Mohlin, Sofie

AU - Vieceli, Felipe Monteleone

AU - Török, Zsofia

AU - Laine, Anni

AU - Westermarck, Jukka

AU - Bronner, Marianne E.

PY - 2018/7/31

Y1 - 2018/7/31

N2 - 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.

AB - 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.

KW - CIP2A

KW - MycN

KW - Neural crest

KW - Neuroblastoma initiation

KW - Sox2

U2 - 10.1073/pnas.1800039115

DO - 10.1073/pnas.1800039115

M3 - Article

VL - 115

SP - E7351-E7360

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 1091-6490

IS - 31

ER -