Epigenetic Disruption of the SLIT-ROBO Interactions in Human Cancer

摘要: During the development of nervous system, guidance cues are required to correctly direct developing axons. These highly conserved in evolution and may have diverse functions receptors. The Slit proteins members these along with their roundabout (robo) receptors, they act as repulsive for robo-expressing axons preventing them from crossing or re-crossing midline. There is increasing evidence that slit-robo interactions not limited axon guidance. effect on due binding mirrored immune system well breast tumour cells; inhibitors cell migration invasion. Our group recently demonstrated both SLIT ROBO genes inactivated human cancers by promoter region CpG island hypermethylation subsequent silencing gene expression. Restoring expression after treatment a demethylating agent, provided further was responsible SLIT-ROBO several cancers. Whilst Robo1 homozygous mutant mice die at birth incomplete lung development, heterozygous show increased predisposition concurrent inactivation remaining wild type allele hypermethylation. SEMA3B, another molecule, be epigenetically suppressed growth. Hence, accumulating role molecules cancer development. Unlike mutational inactivation, epigenetic reversible event. This presents new exciting opportunities clinical management cancer. In addition, increasingly being developed molecular biomarkers non-invasive screens early detection Furthermore, SLIT(s) products secretary proteins, which also lead novel therapeutic approaches. chapter summarises literature families relation diseases.