title: Sox10 controls migration of B16F10 melanoma cells through multiple regulatory target genes.
abstract: It is believed that the inherent differentiation program of melanocytes during embryogenesis predisposes melanoma cells to high frequency of metastasis. Sox10, a transcription factor expressed in neural crest stem cells and a subset of progeny lineages, plays a key role in the development of melanocytes. We show that B16F10 melanoma cells transfected with siRNAs specific for Sox10 display reduced migratory activity which in turn indicated that a subset of transcriptional regulatory target genes of Sox10 is likely to be involved in migration and metastasis of melanoma cells. We carried out a microarray-based gene expression profiling using a Sox10-specific siRNA to identify relevant regulatory targets and found that multiple genes including melanocortin-1 receptor (Mc1r) partake in the regulation of migration. We provide evidences that the effect of Sox10 on migration is mediated in large part by Mitf, a transcription factor downstream to Sox10. Among the mouse melanoma cell lines examined, however, only B16F10 showed robust down-regulation of Sox10 and inhibition of cell migration indicating that further dissection of dosage effects and/or cell line-specific regulatory networks is necessary. The involvement of Mc1r in migration was studied in detail in vivo using a murine metastasis model. Specifically, B16F10 melanoma cells treated with a specific siRNA showed reduced tendency in metastasizing to and colonizing the lung after being injected in the tail vein. These data reveal a cadre of novel regulators and mediators involved in migration and metastasis of melanoma cells that represents potential targets of therapeutic intervention.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Ikjoo
authors.initials: I
authors.lastname: Seong
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Min
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Chang-Yeol
authors.initials: CY
authors.lastname: Yeo
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Kang
authors.forename: Eok-Soo
authors.initials: ES
authors.lastname: Oh
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Hwang
authors.forename: Jaesang
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D055757:SOXE Transcription Factors / Q000378:metabolism*
chemical_list: D051739:Microphthalmia-Associated Transcription Factor; D044102:Receptor, Melanocortin, Type 1; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse