Article
An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogénesis
Author/s | García-Domínguez, Daniel J.
Hontecillas-Prieto, Lourdes Andrés León, Eduardo Sánchez-Molina, Sara Rodríguez-Núñez, Pablo Morón, Francisco J. Hajji, Nabil Mackintosh, Carlos Álava Casado, Enrique de |
Department | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica |
Publication Date | 2020 |
Deposit Date | 2023-06-27 |
Published in |
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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 ... 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. |
Funding agencies | Asociacion Espanola Contra el Cancer (AECC) CIBERONC Consejeria de Salud, Junta de Andalucia European Commission (FP7HEALTH-2011-two-stage) Ministry of Economy and Competitiveness of Spain-FEDER (CIBERONC) |
Project ID. | CB16/12/00361
PI-0197-2016; PI-0013-2018 ID278742 EUROSARC PI11700464; RD06/0020/0059 |
Citation | García-Domínguez, D.J., Hontecillas-Prieto, L., Andrés León, E., Sánchez-Molina, S., Rodríguez-Núñez, P., Morón, F.J.,...,Álava Casado, E.d. (2020). An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogénesis. PLoS ONE, 15 (6), e0234243. https://doi.org/10.1371/journal.pone.0234243. |
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