title: SOX10 promotes melanoma cell invasion by regulating melanoma inhibitory activity.
abstract: The transcription factor SOX10 (SRY (sex determining region Y)-box 10) has a key role in the embryonic development of melanocytes. Recently, it has been suggested that SOX10 is highly relevant for melanoma development and survival. However, the distinct functions and downstream targets of SOX10 in melanoma remain widely unknown. In this study, we inhibited SOX10 via RNA interference in different human melanoma cell lines and found a significantly reduced invasion capacity in vitro and in the chick embryo model. At later time points, SOX10 inhibition reduced proliferation and induced cell death. We identified melanoma inhibitory activity (MIA) as a direct target gene of SOX10, which is an essential protein for melanoma cell migration and invasion. Expression levels of SOX10 and MIA strictly correlated in melanoma cell lines, and SOX10 inhibition reduced MIA expression and promoter activity. Direct binding of SOX10 to the MIA promoter was demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation. Ectopic expression of MIA in SOX10-inhibited melanoma cells restored the invasion capacity, supporting the hypothesis that MIA is responsible for SOX10-mediated melanoma cell invasion. Our data provide evidence for a critical role of SOX10 in melanoma cell invasion through the regulation of MIA and highlight its role as a therapeutic target in melanoma.
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Saskia A
authors.initials: SA
authors.lastname: Graf
authors.affiliation: Section of Dermato-Oncology, Department of Dermatology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Busch
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Besch
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany. Electronic address: carola.berking@med.uni-muenchen.de.
authors.forename: Carola
authors.initials: C
authors.lastname: Berking
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D055757:SOXE Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; D009363:Neoplasm Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors