Histone deacetylase-10 liberates spermidine to support polyamine homeostasis and tumor cell growth
Tracy Murray Stewart, Jackson R. Foley, Cassandra E. Holbert, Glynis Klinke, Gernot Poschet, Raphael R. Steimbach, Aubry K. Miller, Robert A. Casero
Abstract
-AcSpd (at physiological concentrations), which is converted to spermidine and spermine, only in cell lines with HDAC10 activity. Furthermore, we show loss of HDAC10 prevents both restoration of polyamine levels and growth rescue, implicating HDAC10 in supporting polyamine-associated tumor growth. These data suggest the utility of HDAC10-specific inhibitors as an antitumor strategy that may have value in improving the response to polyamine-blocking therapies. Additionally, the cell-based assay developed in this study provides an inexpensive, high-throughput method of screening potentially selective HDAC10 inhibitors.