Along this line, the role of paracrine mediators secreted by tumor cells in regulating melanoma metastasis has been recently reinforced as the binding of the melanoma tumor-secreted protein SPARC to endothelial VCAM drives endothelial permeability and cancer cell extravasation through a ROS-MKK3/6-p38 MAPK pathway [260]. The gene discussed is MAPK1; the disease is cancer.