Slit2 plays a vital role in axon guidance by signaling through Robo receptors. Recent evidence suggests that Slit2 protein may function in other settings because human and Xenopus Slit2 has been shown to inhibit leukocyte chemotaxis. SLIT2 protein is a putative ligand for the ROBO receptors. ROBO1 is inactivated by promoter region hypermethylation in <20% of human cancers. Slit2 is an excellent candidate tumor suppressor gene for colorectal cancer?and that it epigenetically silenced in >40% of lung and breast tumors. SLIT2 promoter region methylation was found in 23 (72%) of 32 primary colorectal cancers. In contrast, normal colorectal mucosa from the same patients exhibited significantly lower levels of SLIT2 promoter region hypermethylation.