The role of FLI-1-EWS, a fusion gene reciprocal to EWS-FLI-1, in Ewing sarcoma
David J. Elzi1, Meihua Song1, Peter J. Houghton1,2,3, Yidong Chen1,2,4 and Yuzuru Shiio1,2,5
1 Greehey Children’s Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas, USA
2 Cancer Therapy and Research Center, The University of Texas Health Science Center, San Antonio, Texas, USA
3 Department of Molecular Medicine, The University of Texas Health Science Center, San Antonio, Texas, USA
4 Department of Epidemiology and Biostatistics, The University of Texas Health Science Center, San Antonio, Texas, USA
5 Department of Biochemistry, The University of Texas Health Science Center, San Antonio, Texas, USA
Correspondence:
Yuzuru Shiio, email:
Keywords: EWS-FLI-1, Ewing sarcoma, FLI-1-EWS
Received: September 14, 2015 Accepted: November 05, 2015 Published: November 07, 2015
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.
