Spotlight on GOT2 in Cancer Metabolism

Abstract

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

Disclosure

C.A.L. has received consulting fees from Astellas Pharmaceuticals, Odyssey Therapeutics, and T-Knife Therapeutics, and is an inventor on patents pertaining to Kras regulated metabolic pathways, redox control pathways in pancreatic cancer, and targeting the GOT1-pathway as a therapeutic approach (US Patent No: 2015126580-A1, 05/07/2015; US Patent No: 20190136238, 05/09/2019; International Patent No: WO2013177426-A2, 04/23/2015). K.B. reports personal fees from Atavistik, outside the submitted work. The authors report no other conflicts of interest in this work.

Additional information

Funding

This work was supported by F99CA264414 (S.A.K.), Cancer Prevention and Research Institute of Texas (CPRIT) award (RR210059) and NIH/NCI (4R00CA248838-02) (J.G-B.), (K.B.), MSK Cancer Center Support Grant/Core Grant P30CA008748 (M.H.S.), R01CA148828 and R01CA245546 (Y.M.S.), and R01CA248160 and R01CA244931 (C.A.L.).