Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma

• Published in: Nature cell biology Vol. 14; no. 8; pp. 882 - 890
• Main Authors: Shakhova, Olga, Zingg, Daniel, Schaefer, Simon M., Hari, Lisette, Civenni, Gianluca, Blunschi, Jacqueline, Claudinot, Stéphanie, Okoniewski, Michal, Beermann, Friedrich, Mihic-Probst, Daniela, Moch, Holger, Wegner, Michael, Dummer, Reinhard, Barrandon, Yann, Cinelli, Paolo, Sommer, Lukas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2012; Nature Publishing Group
• Subjects: 631/80/304; 692/699/67/1813/1634; Animals; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Blotting, Western; Cancer Research; Cell Biology; Cell Line; Cell Line, Tumor; Child; Developmental Biology; Disease Models, Animal; Female; Gene Expression Regulation, Neoplastic; Gene mutations; Genetic aspects; Haploinsufficiency; Health aspects; Humans; Immunohistochemistry; Infant; Laboratory animals; Lesions; letter; Life Sciences; Male; Melanoma; Melanoma - genetics; Melanoma - physiopathology; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Microarray Analysis; Mutation; Nevus - pathology; Nevus - physiopathology; Pathology; Patients; Physiological aspects; Physiology; Real-Time Polymerase Chain Reaction; Risk factors; Skin cancer; SOXE Transcription Factors - genetics; SOXE Transcription Factors - metabolism; Stem Cells; Transcription factors; Switzerland; Germany
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb2535

Shakhova, Sommer and colleagues use mouse models to demonstrate that the Sox10 transcription factor is crucial for the formation and maintenance of giant congenital naevi and melanoma. They show, in human melanoma cells, that Sox10 promotes neural crest stem cell properties, cell proliferation and cell survival. Giant congenital naevi are pigmented childhood lesions that frequently lead to melanoma, the most aggressive skin cancer. The mechanisms underlying this malignancy are largely unknown, and there are no effective therapies. Here we describe a mouse model for giant congenital naevi and show that naevi and melanoma prominently express Sox10, a transcription factor crucial for the formation of melanocytes from the neural crest. Strikingly, Sox10 haploinsufficiency counteracts Nras Q61K -driven congenital naevus and melanoma formation without affecting the physiological functions of neural crest derivatives in the skin. Moreover, Sox10 is also crucial for the maintenance of neoplastic cells in vivo . In human patients, virtually all congenital naevi and melanomas are SOX10 positive. Furthermore, SOX10 silencing in human melanoma cells suppresses neural crest stem cell properties, counteracts proliferation and cell survival, and completely abolishes in vivo tumour formation. Thus, SOX10 represents a promising target for the treatment of congenital naevi and melanoma in human patients.