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Gene Review

SLIT2  -  slit homolog 2 (Drosophila)

Homo sapiens

Synonyms: SLIL3, Slit homolog 2 protein, Slit-2
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Disease relevance of SLIT2


High impact information on SLIT2


Chemical compound and disease context of SLIT2


Biological context of SLIT2


Anatomical context of SLIT2


Associations of SLIT2 with chemical compounds

  • We investigated the roles of netrin-1 and slit-2 in regulation and navigation of dopamine (DA) axon growth using an explant culture preparation of embryonic ventral midbrain (embryonic day 14) and a co-culture system [6].
  • The ability of heparin oligosaccharides of defined structure (ranging in size from disaccharide to tetradeccasaccharide) to inhibit binding of a glypican-Fc fusion protein to recombinant human Slit-2 was determined using an ELISA [8].
  • Exogenous Slit2 does not affect ureteric branching or nephron formation during kidney development [9].
  • We show that Slit2, a neuronal repellent factor, is up-regulated in the skin by allergen sensitization and down-regulates the migration of Langerhans cells [10].
  • Two additional potential leucine-rich repeat encoding exons were identified within intron 12 of Slit2 [11].

Regulatory relationships of SLIT2


Other interactions of SLIT2

  • SLIT2 protein is a putative ligand for the ROBO receptors [1].
  • Both SLIT1 and SLIT2 proteins show approximately 40% amino acid identity to slit and 60% identity to each other [13].
  • Promoter region CpG island of SLIT2 was found to be methylated in 71% (5/7) of glioma cell lines and was unmethylated in five DNA samples from normal brain tissues [2].
  • SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site [14].
  • Upon further elucidation, we observed that Slit-2 mediates the tumor-suppressive effect via a coordinated regulation of the beta-catenin and PI3K signaling pathways and by enhancing beta-catenin/E-cadherin-mediated cell-cell adhesion [15].

Analytical, diagnostic and therapeutic context of SLIT2

  • In addition, SLIT2 expression was downregulated in methylated gliomas relative to unmethylated tumour samples, as demonstrated by quantitative real-time RT-PCR [2].
  • Slit2 appeared to exert inhibitory as well as repulsive effects in the coculture assay [16].
  • Furthermore, recombinant Slit2 can repel embryonic spinal motor axons in cell culture [17].
  • To characterize these interactions in more detail, recombinant human Slit-2 protein and the N- and C-terminal portions generated by in vivo proteolytic processing were used in an enzyme-linked immunosorbent assay to measure the binding of a glypican-Fc fusion protein [18].
  • Time-lapse videomicroscopy indicated that Slit2 reduced medulloblastoma invasion rate without affecting cell direction or proliferation [19].


  1. SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers. Dallol, A., Da Silva, N.F., Viacava, P., Minna, J.D., Bieche, I., Maher, E.R., Latif, F. Cancer Res. (2002) [Pubmed]
  2. Frequent epigenetic inactivation of the SLIT2 gene in gliomas. Dallol, A., Krex, D., Hesson, L., Eng, C., Maher, E.R., Latif, F. Oncogene (2003) [Pubmed]
  3. Comparative genomics on SLIT1, SLIT2, and SLIT3 orthologs. Katoh, Y., Katoh, M. Oncol. Rep. (2005) [Pubmed]
  4. SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells. Dallol, A., Morton, D., Maher, E.R., Latif, F. Cancer Res. (2003) [Pubmed]
  5. Slit2-Mediated chemorepulsion and collapse of developing forebrain axons. Nguyen Ba-Charvet, K.T., Brose, K., Marillat, V., Kidd, T., Goodman, C.S., Tessier-Lavigne, M., Sotelo, C., Chédotal, A. Neuron (1999) [Pubmed]
  6. Netrin-1 and slit-2 regulate and direct neurite growth of ventral midbrain dopaminergic neurons. Lin, L., Rao, Y., Isacson, O. Mol. Cell. Neurosci. (2005) [Pubmed]
  7. Slits contribute to the guidance of retinal ganglion cell axons in the mammalian optic tract. Thompson, H., Barker, D., Camand, O., Erskine, L. Dev. Biol. (2006) [Pubmed]
  8. Structural determinants of heparan sulfate interactions with Slit proteins. Zhang, F., Ronca, F., Linhardt, R.J., Margolis, R.U. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  9. Exogenous Slit2 does not affect ureteric branching or nephron formation during kidney development. Piper, M., Nurcombe, V., Wilkinson, L., Little, M. Int. J. Dev. Biol. (2002) [Pubmed]
  10. Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses. Guan, H., Zu, G., Xie, Y., Tang, H., Johnson, M., Xu, X., Kevil, C., Xiong, W.C., Elmets, C., Rao, Y., Wu, J.Y., Xu, H. J. Immunol. (2003) [Pubmed]
  11. Conserved modularity and potential for alternate splicing in mouse and human Slit genes. Little, M., Rumballe, B., Georgas, K., Yamada, T., Teasdale, R.D. Int. J. Dev. Biol. (2002) [Pubmed]
  12. The migration of cerebellar rhombic lip derivatives. Gilthorpe, J.D., Papantoniou, E.K., Chédotal, A., Lumsden, A., Wingate, R.J. Development (2002) [Pubmed]
  13. Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis. Holmes, G.P., Negus, K., Burridge, L., Raman, S., Algar, E., Yamada, T., Little, M.H. Mech. Dev. (1998) [Pubmed]
  14. SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Grieshammer, U., Le Ma, n.u.l.l., Plump, A.S., Wang, F., Tessier-Lavigne, M., Martin, G.R. Dev. Cell (2004) [Pubmed]
  15. Slit-2 induces a tumor-suppressive effect by regulating beta-catenin in breast cancer cells. Prasad, A., Paruchuri, V., Preet, A., Latif, F., Ganju, R.K. J. Biol. Chem. (2008) [Pubmed]
  16. Axonal growth regulation of fetal and embryonic stem cell-derived dopaminergic neurons by netrin-1 and slits. Lin, L., Isacson, O. Stem Cells (2006) [Pubmed]
  17. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Brose, K., Bland, K.S., Wang, K.H., Arnott, D., Henzel, W., Goodman, C.S., Tessier-Lavigne, M., Kidd, T. Cell (1999) [Pubmed]
  18. Characterization of Slit protein interactions with glypican-1. Ronca, F., Andersen, J.S., Paech, V., Margolis, R.U. J. Biol. Chem. (2001) [Pubmed]
  19. Inhibition of medulloblastoma cell invasion by Slit. Werbowetski-Ogilvie, T.E., Seyed Sadr, M., Jabado, N., Angers-Loustau, A., Agar, N.Y., Wu, J., Bjerkvig, R., Antel, J.P., Faury, D., Rao, Y., Del Maestro, R.F. Oncogene (2006) [Pubmed]
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