A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation
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Author(s)
Kaufman, C. K.
Mosimann, C.
Yang, S.
Thomas, A. J.
Ablain, J.
Tan, J. L.
Fogley, R. D.
van Rooijen, E.
Hagedorn, E. J.
Ciarlo, C.
Date Issued
January 2016
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Kaufman, C. K. et al. “A Zebrafish Melanoma Model Reveals Emergence of Neural Crest Identity during Melanoma Initiation.” Science 351.6272 (2016): aad2197-aad2197.
Version
Author's final manuscript
Abstract
The “cancerized field” concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAF[superscript V600E] mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAF[superscript V600E]-mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1126/science.aad2197
