Molecular targeted therapy in metastatic tumors is rising worldwide.The therapeutic strategy to target the selected EGFR has been developed in clinical trial.However, it shows severe adverse effects in the treatment of patients harboring B-RAFV600E mutation.Although the oral BRAF inhibitors (such as vemurafenib) have remarkable clinical activity in metastatic melanomas with B-RAFV600E mutation, resistance to therapy invariably develops.The limitations of these agents emphasize the importance of developing novel treatment strategies.Our work identifies a novel downstream target of B-RAFV600E, Mpsl.We find that continuously activated B-RAFV600E signaling may be a possible mechanism for the deregulation of Mpsl stability and kinase activity in human tumors,and that persistent phosphorylation of Mps1 through B-RAFV600E signaling is a key event in disrupting the control of centrosome duplication and chromosome stability that may contribute to tumorigenesis.Our findings raise the possibility that targeting the oncogenic B-RAF and S281-phosphorylated Mps1, especially when used in combination could potentially provide great therapeutic opportunities for cancer treatment.Further study need to be done to identify the correlation of B-RAFV600E and Mps1 in Chinese melanoma,colon cancers, and thyroid cancers.Moreover, as Mps1 has been identified as a novel target of B-RAFV600E in patients with melanoma, we will investigate the possibility of a therapeutic role of Mps1 inhibition in patients with B-RAFV600E mutation through retrovirus infection, Mps1 inhibitor, and Mps1 siRNA.