| Literature DB >> 34516843 |
Arianna Baggiolini1, Scott J Callahan1,2,3, Lorenz Studer1,3, Richard M White2,4, Emily Montal2, Joshua M Weiss2,5, Tuan Trieu6,7,8,9, Mohita M Tagore2, Sam E Tischfield10,11,12, Ryan M Walsh1, Shruthy Suresh2, Yujie Fan1,4, Nathaniel R Campbell2,5, Sarah C Perlee2,3, Nathalie Saurat1, Miranda V Hunter2, Theresa Simon-Vermot2, Ting-Hsiang Huang2, Yilun Ma2,5, Travis Hollmann13, Satish K Tickoo13, Barry S Taylor10,11,12,14, Ekta Khurana6,7,8,9, Richard P Koche15.
Abstract
Oncogenes only transform cells under certain cellular contexts, a phenomenon called oncogenic competence. Using a combination of a human pluripotent stem cell–derived cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAFV600E along with additional mutations depends on the intrinsic transcriptional program present in the cell of origin. In both systems, melanocytes are less responsive to mutations, whereas both neural crest and melanoblast populations are readily transformed. Profiling reveals that progenitors have higher expression of chromatin-modifying enzymes such as ATAD2, a melanoma competence factor that forms a complex with SOX10 and allows for expression of downstream oncogenic and neural crest programs. These data suggest that oncogenic competence is mediated by regulation of developmental chromatin factors, which then allow for proper response to those oncogenes.Entities:
Mesh：
Substances：
Year: 2021 PMID： 34516843 PMCID： PMC9440978 DOI： 10.1126/science.abc1048
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714