Open AccessSlit3 inhibits activator protein 1-mediated migration of malignant melanoma cells
Author(s) -
A Denk,
Simone Braig,
Thomas Schubert,
Anja–Katrin Bosserhoff
Publication year - 2011
Publication title -
international journal of molecular medicine
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2011.742
Subject(s) - melanoma , slit , oncogene , biology , activator (genetics) , receptor , microbiology and biotechnology , cancer research , cancer cell , cell cycle , cancer , neuroscience , genetics
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.