Home
/
Data resources
/
Literature
/
22363655
Sox10 controls migration of B16F10 melanoma cells through multiple regulatory target genes.

PLoS One, 2012;7(2):e31477.

Seong I[1], Min HJ, Lee JH, Yeo CY, Kang DM, Oh ES, Hwang ES, Kim J

Affiliations

PMID: 22363655DOI: 10.1371/journal.pone.0031477

Impact factor: 3.752

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.
MeSH terms
Animals; Cell Movement; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Gene Regulatory Networks; Melanoma, Experimental; Mice; Microphthalmia-Associated Transcription Factor; Models, Biological; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; Receptor, Melanocortin, Type 1; Reproducibility of Results; SOXE Transcription Factors
More resources
EndNote: Download