2. Academic Validation
  3. Pyruvate carboxylase and cancer progression

Pyruvate carboxylase and cancer progression

  • Cancer Metab. 2021 Apr 30;9(1):20. doi: 10.1186/s40170-021-00256-7.
Violet A Kiesel # 1,  Madeline P Sheeley # 1,  Michael F Coleman 2,  Eylem Kulkoyluoglu Cotul 3,  Shawn S Donkin 4,  Stephen D Hursting 2 5,  Michael K Wendt 3,  Dorothy Teegarden 6
Affiliations

Affiliations

  • 1 Department of Nutrition Sciences, Purdue University, West Lafayette, IN, 47907, USA.
  • 2 Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, USA.
  • 3 Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, USA.
  • 4 Department of Animal Science, Purdue University, West Lafayette, USA.
  • 5 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA.
  • 6 Department of Nutrition Sciences, Purdue University, West Lafayette, IN, 47907, USA. teegarden@purdue.edu.
  • # Contributed equally.
PMID: 33931119 DOI: 10.1186/s40170-021-00256-7
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.

Keywords

Energy metabolism; Metastasis; Pyruvate carboxylase.

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