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Updated: Apr 18, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Antagonistic cross-regulation between Sox9 and Sox10 controls an anti-tumorigenic program in melanoma

Olga Shakhova1, Phil Cheng2, Pravin J Mishra3

  • 1Cell and Developmental Biology, Institute of Anatomy, University of Zurich, Zurich, Switzerland.

Plos Genetics
|January 29, 2015
PubMed

Insights

The transcription factor SOX10 promotes melanoma, while SOX9 suppresses it. SOX9 upregulation upon SOX10 loss creates a feedback loop, revealing SOX10 and SOX9 as antagonistic melanoma regulators.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Melanoma, a fatal skin cancer, has poorly understood etiology.
  • The transcription factor SOX10 promotes melanoma initiation and progression.
  • Reducing SOX10 expression halts melanoma tumorigenesis by inducing cell cycle exit and apoptosis.

Purpose of the Study:

  • Investigate the role of SOX9 in the anti-tumorigenic effects of SOX10 reduction in melanoma.
  • Elucidate the functional relationship between SOX10 and SOX9 in melanoma development.

Main Methods:

  • Studied SOX9 expression and function in human melanoma cells and a genetic mouse model.
  • Analyzed cell cycle, apoptosis, and gene expression profiles upon SOX9 manipulation.
  • Investigated SOX9 binding to the SOX10 promoter and its effect on SOX10 expression.
  • Assessed the necessity of SOX9 for SOX10-low mediated anti-tumorigenic effects.

Main Results:

  • SOX9 is upregulated upon SOX10 loss and induces cell cycle arrest and apoptosis, similar to SOX10-low melanoma cells.
  • SOX9 binds to the SOX10 promoter, downregulating SOX10 expression and creating a reinforcing feedback loop.
  • SOX9 is essential for the anti-tumorigenic effects observed when SOX10 expression is reduced.
  • Unlike SOX10, SOX9 is not required for normal melanocyte stem cell function or melanoma initiation.

Conclusions:

  • SOX10 and SOX9 act as functionally antagonistic regulators in melanoma development.
  • The SOX10 low/SOX9 high state represents an anti-tumorigenic program.
  • Targeting this SOX10/SOX9 antagonism could offer novel therapeutic strategies for melanoma.

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