Antagonistic cross-regulation between Sox9 and Sox10 controls an anti-tumorigenic program in melanoma

Shakhova, Olga; Cheng, Phil; Mishra, Pravin J; Zingg, Daniel; Schaefer, Simon M; Debbache, Julien; Häusel, Jessica; Matter, Claudia; Guo, Theresa; Davis, Sean; Meltzer, Paul; Mihic-Probst, Daniela; Moch, Holger; Wegner, Michael; Merlino, Glenn; Levesque, Mitchell P; Dummer, Reinhard; Santoro, Raffaella; Cinelli, Paolo; Sommer, Lukas

doi:10.1371/journal.pgen.1004877

Citations

Citation copied

Shakhova, O., Cheng, P., Mishra, P. J., Zingg, D., Schaefer, S. M., Debbache, J., Häusel, J., Matter, C., Guo, T., Davis, S., Meltzer, P., Mihic-Probst, D., Moch, H., Wegner, M., Merlino, G., Levesque, M. P., Dummer, R., Santoro, R., Cinelli, P., & Sommer, L. (2015). Antagonistic cross-regulation between Sox9 and Sox10 controls an anti-tumorigenic program in melanoma. PLoS Genetics, 11(1), e1004877. https://doi.org/10.1371/journal.pgen.1004877

Abstract

Melanoma is the most fatal skin cancer, but the etiology of this devastating disease is still poorly understood. Recently, the transcription factor Sox10 has been shown to promote both melanoma initiation and progression. Reducing SOX10 expression levels in human melanoma cells and in a genetic melanoma mouse model, efficiently abolishes tumorigenesis by inducing cell cycle exit and apoptosis. Here, we show that this anti-tumorigenic effect functionally involves SOX9, a factor related to SOX10 and upregulated in melanoma cells upon lo