title: Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma.
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.
authors: Cell and Developmental Biology, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. olga.shakhova@anatom.uzh.ch
authors: Olga
authors: O
authors: Shakhova
authors: Daniel
authors: D
authors: Zingg
authors: Simon M
authors: SM
authors: Schaefer
authors: Lisette
authors: L
authors: Hari
authors: Gianluca
authors: G
authors: Civenni
authors: Jacqueline
authors: J
authors: Blunschi
authors: Stéphanie
authors: S
authors: Claudinot
authors: Michal
authors: M
authors: Okoniewski
authors: Friedrich
authors: F
authors: Beermann
authors: Daniela
authors: D
authors: Mihic-Probst
authors: Holger
authors: H
authors: Moch
authors: Michael
authors: M
authors: Wegner
authors: Reinhard
authors: R
authors: Dummer
authors: Yann
authors: Y
authors: Barrandon
authors: Paolo
authors: P
authors: Cinelli
authors: Lukas
authors: L
authors: Sommer
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057895:Haploinsufficiency; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009506:Nevus / Q000473:pathology* / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse