The example of Sox10 and Rac1 genes provides detailed illustration of how interfering with these important genes for neural crest development can prevent melanoma formation.
The transcription factor SOX10 mediates the differentiation of neural crest-derived cells, and SOX10 by immunohistochemistry (IHC) is used primarily for the diagnosis of melanoma.
These data further our understanding of SOX10 protein regulation and provide critical information for identification of molecular pathways that modulate SOX10 protein levels in melanoma, with the ultimate goal of discovering novel targets for more effective combinatorial therapeutic approaches for melanoma patients.
These results show that SOX10 is more specific than MART-1 in distinguishing epidermal melanocytes on sun-damaged skin by avoiding overdiagnosis of melanoma.
This is just one of the possible roles of SOX10, which contributes to melanomagenesis by regulating the SOX10-MITF pathway, but also to melanoma cell survival, proliferation and metastasis formation.
This was accompanied by increased expression of E-cadherin, p16, and MC1R and decreased expression of melanoma malignancy markers including SOX10, Nestin, and ABCB5.
Using mutagenesis, co-transfection experiments and chromatin immunoprecipitation, we showed that transcription factors involved in meloe promoter activity in melanomas were the melanocytic specific SOX9 and SOX10 proteins together with the activated P-CREB protein.
We identified melanoma inhibitory activity (MIA) as a direct target gene of SOX10, which is an essential protein for melanoma cell migration and invasion.