EWSR1 and Ewing sarcoma: Expression of SPRY1, a negative feedback inhibitor of the FGFR-activated RAS/MAPK/ERK signaling pathway, was markedly reduced by EWS-FLI1; however, its upregulated expression suppressed cell proliferation and aggressiveness of ES cells by downregulating EWS-FLI1 through the inhibition of RAS/MAPK/ERK activation (Figure 1; Cidre-Aranaz et al., 2017).