Regulation of SOX10 stability via ubiquitination-mediated degradation by Fbxw7α modulates melanoma cell migration.

PMID 26461473


Dysregulation of SOX10 was reported to be correlated with the progression of multiple cancer types, including melanocytic tumors and tumors of the nervous system. However, the mechanisms by which SOX10 is dysregulated in these tumors are poorly understood. In this study, we report that SOX10 is a direct substrate of Fbxw7α E3 ubiquitin ligase, a tumor suppressor in multiple cancers. Fbxw7α promotes SOX10 ubiquitination-mediated turnover through CPD domain of SOX10. Besides, GSK3β phosphorylates SOX10 at CPD domain and facilitates Fbxw7α-mediated SOX10 degradation. Moreover, SOX10 protein levels were inversely correlated with Fbxw7α in melanoma cells, and modulation of Fbxw7α levels regulated the expression of SOX10 and its downstream gene MIA. More importantly, SOX10 reversed Fbxw7α-mediated suppression of melanoma cell migration. This study provides evidence that the tumor suppressor Fbxw7α is the E3 ubiquitin ligase responsible for the degradation of SOX10, and suggests that reduced Fbxw7α might contribute to the upregulation of SOX10 in melanoma cells.