Abstract A48: Metabolic adaptations to serine starvation

Abstract

Abstract Folate dependent one carbon metabolism is essential for cell growth and proliferation and provides building blocks for nucleotide synthesis, NADPH production and methylation of DNA, protein and lipids. The non-essential amino acid serine is an important one-carbon donor and although cells can make serine, many cancer cell lines that have not up-regulated the de novo serine synthesis pathway are dependent on exogenous serine for optimal growth. Indeed, many rapidly proliferating cancer cells take up high quantities of serine from the external environment to support one-carbon metabolism. Using a genetically engineered mouse tumor model, we have now also shown that intestinal tumors in vivo take up more serine than surrounding normal tissue. Through metabolic analysis and by measuring enzyme expression, we investigated how cancer cells adapt to serine starvation. We have found that cells prioritize different metabolic processes during serine starvation, favouring NADPH production over anabolic pathways such as nucleotide synthesis. Citation Format: Christiaan F. Labuschagne, Oliver D.K. Maddocks, Karen H. Vousden. Metabolic adaptations to serine starvation. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A48.