CD73 Protein as a Source of Extracellular Precursors for Sustained NAD+ Biosynthesis in FK866-treated Tumor Cells

Abstract

Background: NAMPT inhibitors showed antitumor activity in preclinical cancer models, but no tumor remission occurred in clinical studies. Results: Cells treated with a NAMPT inhibitor are rescued by low NAD+ e or NAD+ precursors, depending on CD38 and CD73 expression. Conclusion: CD73 enables, whereas CD38 impairs, extracellular NMN utilization by cells for NAD+ biosynthesis. Significance: Combining CD73 and NAMPT inhibition could represent a new anti-cancer strategy. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.