Regulation of Metastasis in Ewing Sarcoma

Simple Summary Ewing sarcoma (EwS) is the second most common bone and soft tissue cancer which mainly happens in children and adolescents. Currently, EwS patients are treated with a combination of surgery, radiation, and interval compressed chemotherapy. While outcomes have improved over the last several decades for patients with localized diseases, little progress has been made in the treatment of patients with newly diagnosed metastatic or relapsed diseases. Moreover, in localized cases, the survival rates are around 70% after five years and 30% after ten years. However, one third of patients develop metastatic tumor and, when metastasis is diagnosed, the five-year survival rates drop sharply to 25%. There is, therefore, urgent need to dissect the regulatory mechanism of EwS tumor metastasis and thus develop treatment strategies to treat metastatic diseases. Here, we reviewed the regulation of metastasis in EwS and hoped this can guide future studies on metastasis. Ewing sarcoma (EwS) is a type of bone and soft tissue tumor in children and adolescents. Over 85% of cases are caused by the expression of fusion protein EWSR1-FLI1 generated by chromosome translocation. Acting as a potent chimeric oncoprotein, EWSR1-FLI1 binds to chromatin, changes the epigenetic states, and thus alters the expression of a large set of genes. Several studies have revealed that the expression level of EWSR1-FLI1 is variable and dynamic within and across different EwS cell lines and primary tumors, leading to tumoral heterogeneity. Cells with high EWSR1-FLI1 expression (EWSR1-FLI1-high) proliferate in an exponential manner, whereas cells with low EWSR1-FLI1 expression (EWSR1-FLI1-low) tend to have a strong propensity to migrate, invade, and metastasize. Metastasis is the leading cause of cancer-related deaths. The continuous evolution of EwS research has revealed some of the molecular underpinnings of this dissemination process. In this review, we discuss the molecular signatures that contribute to metastasis.