Our results suggest that SEMA4 signaling is activated by point mutations in a significant fraction of colorectal tumors, and although specific inhibitors targeting SEMA4 proteins are not currently available, several biological process driven by SEMA4 signaling, such as angiogenesis and invasiveness, could be targeted with FDA approved drugs, including anti-angiogenic agents and MET inhibitors. This evidence concerns the gene MET and colorectal neoplasm.