A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation
Year: 2016
Type: article
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(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.
Source: Science
Authors: Charles K. Kaufman, Christian Mosimann, Zi Peng Fan, Song Yang, Andrew J. Thomas, Julien Ablain, Justin L. Tan, Rachel D. Fogley, Ellen van Rooijen, Elliott J. Hagedorn, Christie Ciarlo, Richard M. White, Dominick A. Matos, Ann-Christin Puller, Cristina Santoriello, Eric C. Liao, Richard A. Young, Leonard I. Zon
Institutions: Boston Children's Hospital, Howard Hughes Medical Institute, Harvard University, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, University of Zurich, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Massachusetts General Hospital, University Medical Center Hamburg-Eppendorf, Kinderkrebs-Zentrum Hamburg, University Cancer Center Hamburg
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Howard Hughes Medical Institute, Ellison Medical Foundation, V Foundation for Cancer Research, European Molecular Biology Organization, Human Frontier Science Program, Melanoma Research Alliance, Helen Hay Whitney Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases
OpenAlex ID: W2268569236