Figure 4.

Role of SHH/Gli cascade in Ewing sarcoma development. Upper panels: EWS-Fli1 protein regulates Gli1 gene expression at the transcriptional level and, therefore, promotes the expression of Gli gene targets implicated in various cellular events, such as cell proliferation and migration. Lower panels: progression of Ewing sarcoma development. During primary tumor growth, cancer cells produce soluble factors, such as growth factors or cytokines, that activate osteoclastogenesis and, in turn, bone degradation. This bone resorption then allows the release of trapped growth factors into the bone matrix able to stimulate tumor growth, “EMT-like” (epithelial mesenchymal transition) angiogenesis and, therefore, the metastatic process.