The Cyr61 expression was correlated with cell migratory potential in osteosarcoma cells, and its upregulation promotes EMT and tumor metastasis in vivo. Moreover, the Cyr61-promoted mesenchymal transition was mediated by the integrin αvβ5, Raf-1, MEK, ERK, and Elk-1 signaling pathways. Here, RAF1 is linked to osteosarcoma.