title: SOX18 Is a Novel Target Gene of Hedgehog Signaling in Cervical Carcinoma Cell Lines.
abstract: Although there is much evidence showing functional relationship between Hedgehog pathway, in particular Sonic hedgehog, and SOX transcription factors during embryonic development, scarce data are available regarding their crosstalk in cancer cells. SOX18 protein plays an important role in promoting tumor angiogenesis and therefore emerged as a promising potential target in antiangiogenic tumor therapy. Recently it became evident that expression of SOX18 gene in tumors is not restricted to endothelium of accompanying blood and lymphatic vessels, but in tumor cells as well.In this paper we have identified human SOX18 gene as a novel target gene of Hedgehog signaling in cervical carcinoma cell lines. We have presented data showing that expression of SOX18 gene is regulated by GLI1 and GLI2 transcription factors, final effectors of Hedgehog signaling, and that modulation of Hedgehog signaling activity in considerably influence SOX18 expression. We consider important that Hedgehog pathway inhibitors reduced SOX18 expression, thus showing, for the first time, possibility for manipulationwith SOX18 gene expression. In addition, we analyzed the role of SOX18 in malignant potential of cervical carcinoma cell line, and showed that its overexpression has no influence on cells proliferation and viability, but substantially promotes migration and invasion of cells in vitro. Pro-migratory effect of SOX18 suggests its role in promoting malignant spreading, possibly in response to Hedgehog activation.
authors.affiliation: Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, P.O.BOX 23, 11000 Belgrade, Serbia.
authors.forename: Isidora
authors.initials: I
authors.lastname: Petrovic
authors.affiliation: Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, P.O.BOX 23, 11000 Belgrade, Serbia.
authors.forename: Milena
authors.initials: M
authors.lastname: Milivojevic
authors.affiliation: Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, P.O.BOX 23, 11000 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Popovic
authors.affiliation: Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, P.O.BOX 23, 11000 Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Schwirtlich
authors.affiliation: Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, P.O.BOX 23, 11000 Belgrade, Serbia.
authors.forename: Branislava
authors.initials: B
authors.lastname: Rankovic
authors.affiliation: Laboratory for Human Molecular Genetics, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, P.O.BOX 23, 11000 Belgrade, Serbia.
authors.forename: Milena
authors.initials: M
authors.lastname: Stevanovic
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015194:Diffusion Chambers, Culture; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055760:SOXF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
chemical_list: C400551:GLI1 protein, human; C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2