title: Slit3 inhibits activator protein 1-mediated migration of malignant melanoma cells.
abstract: The repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. Alterations of the Slit/Robo system have been observed in various pathological conditions and in cancer. However, until today no detailed studies on Slit function on melanoma migration are available. Therefore, we analysed the mRNA expression in melanoma cells and found induction of Robo3 expression compared to normal melanocytes. Functional assays performed with melanoma cells revealed that treatment with Slit3 led to strong inhibition of migration. Interestingly, we observed down-regulation of AP-1 activity and target gene expression after Slit3 treatment contributing to the negative regulation of migration. Taken together, our data showed that Slit3 reduces the migratory activity of melanoma cells, potentially by repulsion of the cells in analogy to the neuronal system. Further studies will be necessary to prove Slit activity in vivo, but due to its function, Slit3 activity may be helpful in the treatment of melanoma.
authors: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors: Alexandra E
authors: AE
authors: Denk
authors: Simone
authors: S
authors: Braig
authors: Thomas
authors: T
authors: Schubert
authors: Anja K
authors: AK
authors: Bosserhoff
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D018808:Transcription Factor AP-1; D000097905:Roundabout Proteins; C432251:Slit3 protein, mouse