Fish Tales: Loss of STAG2 Promotes Migration of Ewing Sarcoma

Abstract

Ewing sarcoma (EwS) is a bone and soft tissue cancer affecting children and adolescents. The most unfavorable prognostic factor of EwS is the presence of metastasis, however this process is still poorly understood. Therefore, we developed a zebrafish xenotransplantation model to better visualize the metastatic behaviour of EwS migration in vivo. STAG2, a cohesin complex subunit mutated in 88% of metastatic EwS cases, appears to promote EwS cell motility. The impact of STAG2 knockout on EwS migration and other mechanisms involved with STAG2 loss and cell migration were evaluated by the knockout of STAG2 in EwS cell lines (A673 and TC71) using CRISPR/Cas9 technology. EwS cell lines were fluorescently labeled prior to xenotransplantation into the larval hindbrain ventricle. STAG2 knockout was determined to promote cell migration in both A673 and TC71 cell lines. STAG2 knockout had a greater effect on EwS cell migration with low EWS-FLI1 expression and moreover, reduced the expression of EWS-FLI1. Therefore, STAG2 loss may contribute to EwS metastasis through regulation of EWS-FLI1 and represent a new biomarker in this disease.