An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
PloS one - 15(2020), 6 vom: 05., Seite e0234243 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
García-Domínguez, Daniel J [VerfasserIn] |
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| Links: |
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| Themen: |
9007-49-2 |
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| Anmerkungen: |
Date Completed 24.08.2020 Date Revised 24.08.2020 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0234243 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310817536 |
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| 100 | 1 | |a García-Domínguez, Daniel J |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An inducible ectopic expression system of EWSR1-FLI1 as a tool for understanding Ewing sarcoma oncogenesis |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 24.08.2020 | ||
| 500 | |a Date Revised 24.08.2020 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Oncogene Proteins, Fusion |2 NLM | |
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| 700 | 1 | |a Hontecillas-Prieto, Lourdes |e verfasserin |4 aut | |
| 700 | 1 | |a León, Eduardo Andrés |e verfasserin |4 aut | |
| 700 | 1 | |a Sánchez-Molina, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Rodríguez-Núñez, Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a Morón, Francisco J |e verfasserin |4 aut | |
| 700 | 1 | |a Hajji, Nabil |e verfasserin |4 aut | |
| 700 | 1 | |a Mackintosh, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a de Álava, Enrique |e verfasserin |4 aut | |
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