Pyruvate carboxylase and cancer progression

• Published in: Cancer & metabolism Vol. 9; no. 1; pp. 20 - 13
• Main Authors: Kiesel, Violet A., Sheeley, Madeline P., Coleman, Michael F., Cotul, Eylem Kulkoyluoglu, Donkin, Shawn S., Hursting, Stephen D., Wendt, Michael K., Teegarden, Dorothy
• Format: Journal Article
• Language: English
• Published: London BioMed Central 30.04.2021; BioMed Central Ltd; BMC
• Subjects: Adipocytes; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer; Cancer Research; Cell Biology; Development and progression; Dextrose; Energy; Energy metabolism; Enzymes; Fatty acids; Glucose; Glutamine; Homeostasis; Imaging; Insulin; Liver; Lung cancer; Metabolic Diseases; Metabolism; Metabolomics; Metastasis; Oncology; Oxidative stress; Pancreatic beta cells; Physiological aspects; Prevention; Pyruvate carboxylase; Radiology; Review; Transcription factors; Tumorigenesis; Energy metabolism; Pyruvate carboxylase; Metastasis
• ISSN: 2049-3002; 2049-3002
• DOI: 10.1186/s40170-021-00256-7

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.