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- Title
An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis.
- Authors
García-Domínguez, Daniel J.; Hontecillas-Prieto, Lourdes; León, Eduardo Andrés; Sánchez-Molina, Sara; Rodríguez-Núñez, Pablo; Morón, Francisco J.; Hajji, Nabil; Mackintosh, Carlos; de Álava, Enrique
- Abstract
The presence of the chimeric EWSR1-FLI1 oncoprotein is the main and initiating event defining Ewing sarcoma (ES). The dysregulation of epigenomic and proteomic homeostasis induced by the oncoprotein contributes to a wide variety of events involved in oncogenesis and tumor progression. Attempts at studying the effects of EWSR1-FLI1 in non-tumor cells to understand the mechanisms underlying sarcomagenesis have been unsuccessful to date, as ectopic expression of EWSR1-FLI1 blocks cell cycle progression and induces apoptosis in the tested cell lines. Therefore, it is essential to find a permissive cell type for EWSR1-FLI1 expression that allows its endogenous molecular functions to be studied. Here we have demonstrated that HeLa cell lines are permissive to EWSR1-FLI1 ectopic expression, and that our model substantially recapitulates the endogenous activity of the EWSR1-FLI1 fusion protein. This model could contribute to better understanding ES sarcomagenesis by helping to understand the molecular mechanisms induced by the EWSR1-FLI1 oncoprotein.
- Subjects
EWING'S sarcoma; CHIMERIC proteins; CELL cycle; HELA cells; CELL lines; EPIGENOMICS
- Publication
PLoS ONE, 2020, Vol 15, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0234243