Journal article
Modeling the Initiation of Ewing Sarcoma Tumorigenesis in Differentiating Human Embryonic Stem Cells
Oncogene, Vol.35(24), pp.3092-3102
10/12/2015
DOI: 10.1038/onc.2015.368
PMCID: PMC4829493
PMID: 26455317
Abstract
Oncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. However, despite the well-established role of EWS-FLI1 in tumor initiation, the development of models of Ewing sarcoma in human cells with defined genetic elements has been challenging. Here, we report a novel approach to model the initiation of Ewing sarcoma tumorigenesis that exploits the developmental and pluripotent potential of human embryonic stem cells. The inducible expression of EWS-FLI1 in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. Furthermore, these cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth, which is a hallmark Ewing sarcoma tumors.
Details
- Title: Subtitle
- Modeling the Initiation of Ewing Sarcoma Tumorigenesis in Differentiating Human Embryonic Stem Cells
- Creators
- David J. Gordon - Dana-Farber Cancer InstituteMona Motwani - University of Massachusetts Chan Medical SchoolDavid Pellman - Dana-Farber Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.35(24), pp.3092-3102
- DOI
- 10.1038/onc.2015.368
- PMID
- 26455317
- PMCID
- PMC4829493
- NLM abbreviation
- Oncogene
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Language
- English
- Date published
- 10/12/2015
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984354151202771
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