Improper regulation of SOX9 or SOX10 is also associated with cancerous transformation, and thus understanding the normal function of SOX proteins in the melanocyte will be key to revealing how these proteins contribute to melanoma.
SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P=0.008).
As cell-cycle dysregulation is a core event in neoplastic transformation, the role for SOX10 in maintaining cell-cycle control in melanocytes suggests a rational new direction for targeted treatment or prevention of melanoma.
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.
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.
We identified melanoma inhibitory activity (MIA) as a direct target gene of SOX10, which is an essential protein for melanoma cell migration and invasion.
Somatic mutations in SOX10, a transcription factor, which acts upstream of microphthalmia-associated transcription factor and synergizes with microphthalmia-associated transcription factor, was identified in some melanoma cell lines.
In addition, SAMMSON is a target of the lineage-specific transcription factor SOX10 and its expression is detectable in more than 90% of human melanomas.
Our findings provide novel insights into the regulatory mechanisms of melanocyte proliferation and may have implications for our understanding of the roles of SOX10 and MCM5 in abnormal melanocyte proliferation disorders such as cutaneous melanoma.
Finally, CONPs obviously suppressed the growth of human melanoma in tumor-bearing nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice, accompanied with tumors structural necrosis and fibrosis remarkably and decreased expression of CD271, SOX10 and MITF.
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.
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.