Histone deacetylase-10 liberates spermidine to support polyamine homeostasis and tumor cell growth.

ABSTRACT: Cytosolic histone deacetylase-10 (HDAC10) specifically deacetylates the modified polyamine N⁸-acetylspermidine (N⁸-AcSpd). Although intracellular concentrations of N⁸-AcSpd are low, extracellular sources can be abundant, particularly in the colonic lumen. Extracellular polyamines, including those from the diet and microbiota, can support tumor growth both locally and at distant sites. However, the contribution of N⁸-AcSpd in this context is unknown. We hypothesized that HDAC10, by converting N⁸- AcSpd to spermidine, may provide a source of this growth-supporting polyamine in circumstances of reduced polyamine biosynthesis, such as in polyamine-targeting anticancer therapies. Inhibitors of polyamine biosynthesis, including α-difluoromet

SUBMITTER: Stewart TM 

PROVIDER: S-EPMC9486564 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature