摘要
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 forgiant congenital naevi and show that naevi and melanoma prominently express Sox 10, a transcription factor crucial for the formation of melanocytes from the neural crest. Strikingly, Sox 10 haploinsufficiency counteracts Nras(Q61K)-driven congenital naevus and melanoma formation without affecting the physiological functions of neural crest derivatives in the skin. Moreover, Sox 10 is also crucial for the maintenance of neoplastic cells in vivo. In human patients, virtually all congenital naevi and melanomas are SOX 10 positive. Furthermore, SOX 10 silencing in human melanoma cells suppresses neural crest stem cell properties, counteracts proliferation and cells urvival, and completely abolishes in vivo tumour formation. Thus, SOX 10 represents a promising target for the treatment of congenital naevi and melanoma in human patient.
- 出版日期2012-8