Abstract 1743: SOX10 is required for cell cycle regulation and melanomagenesis.

The transcription factor SOX10 is essential for proper survival and differentiation of neural crest cell lineages, and plays an important role in the establishment and maintenance of melanocytes. SOX10 is also highly expressed in melanoma tumors, however its role in the progression of the disease is not yet understood. Here, we report that melanoma tumor cell lines require wild-type SOX10 expression for proliferation, and detail the rescue of melanoma in the metabotropic glutamate receptor 1 (Grm1Tg) transgenic mouse by Sox10 haploinsufficiency. Stable SOX10 knockdown in human melanoma cells results in arrested growth, altered cellular morphology, and senescence. Cells with a stable loss of SOX10 are arrested in the G1 phase of the cell cycle with elevated cyclin-dependent kinase inhibitor 1A and 1B (p21 and p27) expression. SOX10 loss also results in hypophosphorylation of retinoblastoma protein (RB) and a reduction in the expression of its binding partner E2F1. Previously, the RB-E2F1 pathway has been shown to play a central role in cell cycle regulation, and here we demonstrate that SOX10 expression is required for the maintenance of the RB-E2F1 pathway to promote melanoma cell growth. One of the main events driving cellular transformation is the dysregulation of the cell cycle, therefore the role that SOX10 has in maintaining this process provides great promise for targeted interventions. Citation Format: Julia C. Cronin, Dawn E. Watkins-Chow, Art Incao, Joanne H. Hasskamp, Nicola Schonewolf, Nicholas K. Hayward, Boris C. Bastian, Reinhard Dummer, Stacie K. Loftus, William J. Pavan. SOX10 is required for cell cycle regulation and melanomagenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1743. doi:10.1158/1538-7445.AM2013-1743