The Role of FLI-1-EWS, a Fusion Gene Reciprocal to EWS-FLI-1, in Ewing Sarcoma

Overview

Journal Genes Cancer

Specialty Oncology

Date 2016 Jan 26

PMID 26807198

Citations 21

Authors

David J Elzi

Meihua Song

Peter J Houghton

Yidong Chen

Yuzuru Shiio

Affiliations

Soon will be listed here.

Abstract

Ewing sarcoma is a cancer of bone and soft tissue in children that is characterized by a chromosomal translocation involving EWS and an Ets family transcription factor, most commonly FLI-1. The EWS-FLI-1 fusion oncogene is widely believed to play a central role in Ewing sarcoma. The EWS-FLI-1 gene product regulates the expression of a number of genes important for cancer progression, can transform mouse cells such as NIH3T3 and C3H10T1/2, and is necessary for proliferation and tumorigenicity of Ewing sarcoma cells, suggesting that EWS-FLI-1 is the causative oncogene. However, a variety of evidence also suggest that EWS-FLI-1 alone cannot fully explain the Ewing sarcomagenesis. Here we report that FLI-1-EWS, a fusion gene reciprocal to EWS-FLI-1, is frequently expressed in Ewing sarcoma. We present evidence suggesting that endogenous FLI-1-EWS is required for Ewing sarcoma growth and that FLI-1-EWS cooperates with EWS-FLI-1 in human mesenchymal stem cells, putative cells of origin of Ewing sarcoma, through abrogation of the proliferation arrest induced by EWS- FLI-1.

Citing Articles

Ewing sarcoma from molecular biology to the clinic.

Dupuy M, Lamoureux F, Mullard M, Postec A, Regnier L, Baudhuin M Front Cell Dev Biol. 2023; 11:1248753.

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Human EWS-FLI protein recapitulates in Drosophila the neomorphic functions that induce Ewing sarcoma tumorigenesis.

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Regulation of EWSR1-FLI1 Function by Post-Transcriptional and Post-Translational Modifications.

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Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.

Orth M, Surdez D, Faehling T, Ehlers A, Marchetto A, Grossetete S Cell Rep. 2022; 41(10):111761.

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