Additionally, EWS-FLI1 and EZH2, whose mRNAs have been shown to be shed from the tumor cells as an exosome cargo [183,184], may not only bind and block RUNX2 in the tumor cells [185] but also prohibit osteoblast differentiation of mesenchymal cells in the tumor stroma, thus shifting the homeostatic balance in the metastatic bone niche to osteoclast activation. The gene discussed is EWSR1; the disease is neoplasm.