A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation
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A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. / Kaufman, Charles K; Mosimann, Christian; Fan, Zi Peng; Yang, Song; Thomas, Andrew J; Ablain, Julien; Tan, Justin L; Fogley, Rachel D; van Rooijen, Ellen; Hagedorn, Elliott J; Ciarlo, Christie; White, Richard M; Matos, Dominick A; Puller, Ann-Christin; Santoriello, Cristina; Liao, Eric C; Young, Richard A; Zon, Leonard I.
In: SCIENCE, Vol. 351, No. 6272, 29.01.2016, p. aad2197.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation
AU - Kaufman, Charles K
AU - Mosimann, Christian
AU - Fan, Zi Peng
AU - Yang, Song
AU - Thomas, Andrew J
AU - Ablain, Julien
AU - Tan, Justin L
AU - Fogley, Rachel D
AU - van Rooijen, Ellen
AU - Hagedorn, Elliott J
AU - Ciarlo, Christie
AU - White, Richard M
AU - Matos, Dominick A
AU - Puller, Ann-Christin
AU - Santoriello, Cristina
AU - Liao, Eric C
AU - Young, Richard A
AU - Zon, Leonard I
N1 - Copyright © 2016, American Association for the Advancement of Science.
PY - 2016/1/29
Y1 - 2016/1/29
N2 - 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(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(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.
AB - 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(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(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.
KW - Animals
KW - Animals, Genetically Modified
KW - Carcinogenesis
KW - Embryonic Stem Cells
KW - Enhancer Elements, Genetic
KW - Gene Expression Regulation, Developmental
KW - Gene Expression Regulation, Neoplastic
KW - Genes, Reporter
KW - Green Fluorescent Proteins
KW - Melanocytes
KW - Melanoma
KW - Melanoma, Experimental
KW - Mutation
KW - Nerve Tissue Proteins
KW - Neural Crest
KW - Proto-Oncogene Proteins B-raf
KW - SOXE Transcription Factors
KW - Skin Neoplasms
KW - Tumor Suppressor Protein p53
KW - Zebrafish
KW - Zebrafish Proteins
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1126/science.aad2197
DO - 10.1126/science.aad2197
M3 - SCORING: Journal article
C2 - 26823433
VL - 351
SP - aad2197
JO - SCIENCE
JF - SCIENCE
SN - 0036-8075
IS - 6272
ER -