CD38 Inhibits Prostate Cancer Metabolism and Proliferation by Reducing Cellular NAD⁺ Pools.

ABSTRACT: Tumor cells require increased rates of cell metabolism to generate the macromolecules necessary to sustain proliferation. They rely heavily on NAD⁺ as a cofactor for multiple metabolic enzymes in anabolic and catabolic reactions. NAD⁺ also serves as a substrate for PARPs, sirtuins, and cyclic ADP-ribose synthases. Dysregulation of the cyclic ADP-ribose synthase CD38, the main NAD'ase in cells, is reported in multiple cancer types. This study demonstrates a novel connection between CD38, modulation of NAD⁺, and tumor cell metabolism in prostate cancer. CD38 expression inversely correlates with prostate cancer progression. Expressing CD38 in prostate cancer cells lowered intracellular NAD⁺, resulting in cell-cycle arrest and expression of p21^C

SUBMITTER: Chmielewski JP 

PROVIDER: S-EPMC6214722 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature