Abstract 1522: Survival of skin cancer tumor initiating cells requires the Ezh2 polycomb group protein

Abstract Epidermal squamous cell carcinoma is among the most common cancers in humans. These tumors are comprised of phenotypically diverse of cells that display varying potential for proliferation and differentiation. Polycomb group (PcG) proteins, including Ezh2, are important candidate stem cell maintanence proteins. Our previous study showed that Ezh2-enriched epidermal cancer stem cells (ECS cells) represent a minority of cells in tumors, yet drive aggressive tumor formation. In the present study, we show that Ezh2 is required for ECS cell survival, migration, invation and tumor formatiom and this is associated with increased histone H3 trimethylationon lysine 27, a mark of Ezh2 action. We also show that Ezh2 knockdown or treatment with Ezh2-selective inhibitors, GSK126 or EP-6438, reduce Ezh2 level and activity, leading to reduced spheroid formation, migration, invasion and tumor formation. Use of these inhibitors was associated with reduced ECS cell vaibility and induction of apoptosis. These studies indicate that epidermal squamous cell carcinoma cells contain a subpopulation of cancer stem cells-like tumor initiating cells that are enriched in Ezh2 expression and that Ezh2 is required for optimal survival of these cells and tumor formation. These studies suggest that treatment with Ezh2 inhibitors may be a strategy for reducing epidermal cancer stem cell survival and supressing tumor formation. Citation Format: Gautam Adhikary, Dan Grun, Candace Kerr, Sivaprakasam Balasubramanian, Ellen Rorke, Wen Xu, Richard Eckert. Survival of skin cancer tumor initiating cells requires the Ezh2 polycomb group protein. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1522. doi:10.1158/1538-7445.AM2015-1522