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

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For the development of future cancer therapies it is imperative to understand the molecular processes underlying tumor initiation and expansion. Many key factors involved in these processes have been identified based on cell culture and transplantation experiments, but their relevance for tumor formation and disease progression in the living organism is often unclear. Therefore, genetically modified mice spontaneously developing tumors present indispensable models for cancer research. Here, we address this issue by studying the formation of melanoma, the most fatal skin tumor in industrialized countries. To this end, we use a transgenic mouse model to elucidate cellular and molecular mechanisms regulating congenital nevus and melanoma initiation. We show that a transcription factor called SOX10 promotes melanoma formation by repressing an anti-tumorigenic program involving the activity of a related factor, SOX9. When SOX10 is inactivated, SOX9 becomes upregulated and induces cell cycle arrest and death in melanoma cells. Furthermore, upon experimental elevation of SOX9 levels, SOX10 activity is suppressed, revealing an antagonistic relationship between SOX9 and SOX10 in melanoma initiation. Knowledge of how an anti-tumorigenic program can be stimulated by modulating the activities of these key factors might help to design novel therapeutic strategies.

Vyšlo v časopise: Antagonistic Cross-Regulation between Sox9 and Sox10 Controls an Anti-tumorigenic Program in Melanoma. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004877
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004877

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