Pyruvate carboxylase and cancer progression

Cancer & Metabolism

Shawn S. Donkin¹  Eylem Kulkoyluoglu Cotul²  Michael K. Wendt²  Violet A. Kiesel³  Dorothy Teegarden³  Madeline P. Sheeley³  Stephen D. Hursting⁴  Michael F. Coleman⁴ 

[1] Department of Animal Science, Purdue University;Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University;Department of Nutrition Sciences, Purdue University;Department of Nutrition, University of North Carolina at Chapel Hill;

关键词: Pyruvate carboxylase;    Metastasis;    Energy metabolism;   

DOI  :  10.1186/s40170-021-00256-7

来源: DOAJ

【 摘 要 】

Abstract Pyruvate carboxylase (PC) is a mitochondrial enzyme that catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate (OAA), serving to replenish the tricarboxylic acid (TCA) cycle. In nonmalignant tissue, PC plays an essential role in controlling whole-body energetics through regulation of gluconeogenesis in the liver, synthesis of fatty acids in adipocytes, and insulin secretion in pancreatic β cells. In breast cancer, PC activity is linked to pulmonary metastasis, potentially by providing the ability to utilize glucose, fatty acids, and glutamine metabolism as needed under varying conditions as cells metastasize. PC enzymatic activity appears to be of particular importance in cancer cells that are unable to utilize glutamine for anaplerosis. Moreover, PC activity also plays a role in lipid metabolism and protection from oxidative stress in cancer cells. Thus, PC activity may be essential to link energy substrate utilization with cancer progression and to enable the metabolic flexibility necessary for cell resilience to changing and adverse conditions during the metastatic process.

【 授权许可】

Unknown