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Sox2 is dispensable for primary melanoma and metastasis formation

Oncogene volume 36, pages 4516–4524 (2017)Cite this article

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Abstract

Tumor initiation and metastasis formation in many cancers have been associated with emergence of a gene expression program normally active in embryonic or organ-specific stem cells. In particular, the stem cell transcription factor Sox2 is not only expressed in a variety of tumors, but is also required for their formation. Melanoma, the most aggressive skin tumor, derives from melanocytes that during development originate from neural crest stem cells. While neural crest stem cells do not express Sox2, expression of this transcription factor has been reported in melanoma. However, the role of Sox2 in melanoma is controversial. To study the requirement of Sox2 for melanoma formation, we therefore performed CRISPR-Cas9-mediated gene inactivation in human melanoma cells. In addition, we conditionally inactivated Sox2 in a genetically engineered mouse model, in which melanoma spontaneously develops in the context of an intact stroma and immune system. Surprisingly, in both models, loss of Sox2 did neither affect melanoma initiation, nor growth, nor metastasis formation. The lack of a tumorigenic role of Sox2 in melanoma might reflect a distinct stem cell program active in neural crest stem cells and during melanoma formation.

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Acknowledgements

We thank Annika Klug for help with hematoxylin and eosin stainings and Jessica Häusel for assistance in histology. We would like to thank Daniel Zingg for his help with statistical analysis. Further, we acknowledge the advice by the Cancer Biology PhD program of the University of Zurich. This work was supported by the Swiss National Science Foundation (SNF), the University Research Priority Program (URPP) ‘Translational Cancer Research’ Biobank, and the Swiss Cancer League. Work in the Nicolis laboratory was supported by AIRC and Telethon.

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Authors and Affiliations

  1. Institute of Anatomy, University of Zurich, Zurich, Switzerland

    S M Schaefer, C Segalada, M Bonalli, V Parfejevs & L Sommer

  2. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

    P F Cheng, M P Levesque & R Dummer

  3. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy

    S K Nicolis

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Correspondence to L Sommer.

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Schaefer, S., Segalada, C., Cheng, P. et al. Sox2 is dispensable for primary melanoma and metastasis formation. Oncogene 36, 4516–4524 (2017). https://doi.org/10.1038/onc.2017.55

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