An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis.

Garcia-Dominguez, Daniel JHontecillas-Prieto, LourdesLeon, Eduardo AndresSanchez-Molina, SaraRodriguez-Nuñez, PabloMoron, Francisco JHajji, NabilMackintosh, Carlosde-Alava, Enrique2023-02-092023-02-092020-06-05García-Domínguez DJ, Hontecillas-Prieto L, León EA, Sánchez-Molina S, Rodríguez-Núñez P, Morón FJ, et al. An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis. PLoS One. 2020 Jun 5;15(6):e0234243.http://hdl.handle.net/10668/15686The 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Binding SitesDNAHeLa CellsOncogene Proteins, FusionCarcinogenesisEctopic Gene ExpressionHumansSarcoma, EwingAn inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis.research article32502203open accessProteínas oncogénicasExpresión génica ectópicaCélulasNeoplasiasHomeostasisApoptosisCarcinogénesis10.1371/journal.pone.02342431932-6203PMC7274397https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0234243&type=printablehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274397/pdf