Open AccessAn inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis
Author(s) -
Daniel J. García-Domínguez,
Lourdes Hontecillas-Prieto,
Eduardo Andrés-León,
Sara Sánchez-Molina,
Pablo RodríguezNúñez,
Francisco José Morón,
Nabil Hajji,
Carlos Mackintosh,
Enrique de Álava
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0234243
Subject(s) - ectopic expression , fli1 , biology , carcinogenesis , microbiology and biotechnology , cancer research , cell cycle , cell growth , cell , cell culture , cancer , genetics , transcription factor , gene
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.