Cadherin-11 contributes to the heterogenous and dynamic Wnt-Wnt-ß-catenin pathway activation in Ewing sarcoma

Ewing sarcoma (ES) is the second most common bone cancer in children, and while patients who present with metastatic disease at the time of diagnosis have a dismal prognosis. ES tumors are driven by the fusion gene EWS/Fli1, and while these tumor are genetically homogenous, the transcriptional heterogeneity can lead to a variety of cellular processes including metastasis. In this study, we demonstrate that in ES cells, the canonical Wnt/?-Catenin signaling pathway is heterogeneously activated in vitro and in vivo, correlating with hypoxia and EWS/Fli1 activity. Overall design: A4573 cells were implanted orthotopically in the pretibial space of mice followed by single cell RNA-seq