Spotlight on GOT2 in Cancer Metabolism

Samuel A Kerk,1 Javier Garcia-Bermudez,2 Kivanc Birsoy,3 Mara H Sherman,4 Yatrik M Shah,5 Costas A Lyssiotis5 1Doctoral Program in Cancer Biology, University of Michigan, Ann Arbor, MI, USA; 2Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Laboratory of Metabolic Regulation and Genetics, The Rockefeller University, New York, NY, USA; 4Cancer Biology & Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 5Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USACorrespondence: Costas A Lyssiotis, Email clyssiot@med.umich.eduAbstract: GOT2 is at the nexus of several critical metabolic pathways in homeostatic cellular and dysregulated cancer metabolism. Despite this, recent work has emphasized the remarkable plasticity of cancer cells to employ compensatory pathways when GOT2 is inhibited. Here, we review the metabolic roles of GOT2, highlighting findings in both normal and cancer cells. We emphasize how cancer cells repurpose cell intrinsic metabolism and their flexibility when GOT2 is inhibited. We close by using this framework to discuss key considerations for future investigations into cancer metabolism.Keywords: transaminase, mitochondria, tumor microenvironment, nucleotides, redox, pancreatic cancer