Functional studies showed that SNAIL1 (SNAI1) is activated downstream of ICN1 in human ERMS and stimulated self-renewal and growth, in part, by repressing expression of the muscle differentiation transcription factor MEF2C. Our data provide a mechanism by which oncogenic NOTCH1 regulates the overall number and properties of tumor-sustaining cell types in ERMS and provides therapeutic targets for this disease. The gene discussed is SNAI1; the disease is neoplasm.