Antagonistic Cross-Regulation between Sox9 and Sox10 Controls an Anti-tumorigenic Program in Melanoma

• DOI: 10.1371/journal.pgen.1004877
• Publication Date: 2015-01-28T18:59:57Z
• Authors: Olga Shakhova; Phil Cheng; Pravin J. Mishra; Daniel Zingg; Simon M. Schaefer; Julien Debbache; Jessica Häusel; Claudia Matter; Theresa Guo; Sean Davis; Paul Meltzer; Daniela Mihic-Probst; Holger Moch; Michael Wegner; Glenn Merlino; Mitchell P. Levesque; Reinhard Dummer; Raffaella Santoro; Paolo Cinelli; Lukas Sommer
• Keywords: SOX10; SOX9; Melanocyte

Melanoma is the most fatal skin cancer, but etiology of this devastating disease still poorly understood. Recently, transcription factor Sox10 has been shown to promote both melanoma initiation and progression. Reducing SOX10 expression levels in human cells a genetic mouse model, efficiently abolishes tumorigenesis by inducing cell cycle exit apoptosis. Here, we show that anti-tumorigenic effect functionally involves SOX9, related upregulated upon loss SOX10. Unlike SOX10, SOX9 not required for normal melanocyte stem function, formation hyperplastic lesions, initiation. To contrary, overexpression results arrest, apoptosis, gene profile shared with reduced expression. Moreover, binds promoter induces downregulation expression, revealing feedback loop reinforcing low/SOX9 high ant,m/ii-tumorigenic program. Finally, vitro vivo achieved reducing Thus, are antagonistic regulators development.