The "Ideal" Target's Network: Factors Modulating EWS-FLI1 Expression and Function in Ewing's Sarcoma

EWS-FLI1 is a chimeric transcription factor that results from gene fusion as a consequence of chromosomal translocation exclusively in Ewing's sarcoma family tumors (ESFT). Recent genomic studies have identified a network of EWS-FLI1 regulated genes and functions. These studies mainly relied on experimentally modulating EWS-FLI1 expression in ESFT cell lines under standard in vitro growth conditions (21% oxygene, monolayer culture). In vivo, solid tumors grow as three-dimensional structures and are frequently hypoxic. We find that two-thirds of primary ESFT express hypoxia inducible factor HIF-1α consistent with…