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

Details

Serval ID
serval:BIB_374DAFD4D9B0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma.
Journal
Nature Cell Biology
Author(s)
Shakhova O., Zingg D., Schaefer S.M., Hari L., Civenni G., Blunschi J., Claudinot S., Okoniewski M., Beermann F., Mihic-Probst D., Moch H., Wegner M., Dummer R., Barrandon Y., Cinelli P., Sommer L.
ISSN
1476-4679 (Electronic)
ISSN-L
1465-7392
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
14
Number
8
Pages
882-890
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
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.
Keywords
Animals, Blotting, Western, Cell Line, Cell Line, Tumor, Child, Disease Models, Animal, Female, Gene Expression Regulation, Neoplastic, Haploinsufficiency, Humans, Immunohistochemistry, Infant, Male, Melanoma/genetics, Melanoma/physiopathology, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Microarray Analysis, Nevus/pathology, Nevus/physiopathology, Real-Time Polymerase Chain Reaction, SOXE Transcription Factors/genetics, SOXE Transcription Factors/metabolism, Tumor Markers, Biological/genetics, Tumor Markers, Biological/metabolism
Pubmed
Web of science
Create date
21/01/2013 11:48
Last modification date
20/08/2019 13:25
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