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. Here, RUNX2 is linked to neoplasm.