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Sox10 controls migration of B16F10 melanoma cells through multiple regulatory target genes

Title
Sox10 controls migration of B16F10 melanoma cells through multiple regulatory target genes
Authors
Seong I.Min H.J.Lee J.-H.Yeo C.-Y.Kang D.M.Oh E.-S.Hwang E.S.Kim J.
Ewha Authors
오억수김재상여창열황은숙강동민
SCOPUS Author ID
오억수scopus; 김재상scopus; 여창열scopus; 황은숙scopus; 강동민scopus
Issue Date
2012
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 7, no. 2
Indexed
SCIE; SCOPUS WOS scopus
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. © 2012 Seong et al.
DOI
10.1371/journal.pone.0031477
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자연과학대학 > 생명과학전공 > Journal papers
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