Although many diverse processes are described to drive the metastatic development of ES, multiple studies report the crucial role of the EWS-FLI1 fusion protein in intra-tumor heterogeneity and in the ability of cells to migrate to metastatic sites (Franzetti et al., 2017; Sheffield et al., 2017; Aynaud et al., 2020). Here, EWSR1 is linked to Ewing sarcoma.