Mitochondrial pyruvate carrier 1 expression controls cancer epithelial-mesenchymal transition and radioresistance

Cancer Sci. 2019 Apr;110(4):1331-1339. doi: 10.1111/cas.13980.

Abstract

Mitochondrial pyruvate carrier (MPC) is known to cause different expressions in normal and cancer cells. We observed a change in phenotype with the suppression of MPC expression. We knocked down MPC1 and/or MPC2 using siRNA or shRNA. We observed its cell morphology and accompanying molecular marker. Furthermore, the radioresistance of the MPC knockdown cell line was examined using a colony formation assay. MPC1-suppressed cells changed their morphology to a spindle shape. Epithelial-mesenchymal transition (EMT) was suspected, and examination of the EMT marker by PCR showed a decrease in E-cadherin and an increase in fibronectin. Focusing on glutamine metabolism as the mechanism of this phenomenon, we knocked down the glutamine-metabolizing enzyme glutaminase (GLS). EMT was also observed in GLS-suppressed cells. Furthermore, when MPC1-suppressed cells were cultured in a glutamine-deficient medium, changes in EMT markers were suppressed. In addition, MPC1-suppressed cells also increased with a significant difference in radioresistance. Decreased MPC1 expression favorably affects EMT and radioresistance of cancer.

Keywords: EMT; glutamine; metabolism; mitochondria pyruvate career; radiation therapy.

MeSH terms

  • Biomarkers
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins / genetics*
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Models, Biological
  • Monocarboxylic Acid Transporters
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neoplasms / radiotherapy
  • Radiation Tolerance / genetics*

Substances

  • Biomarkers
  • MPC1 protein, human
  • Mitochondrial Membrane Transport Proteins
  • Monocarboxylic Acid Transporters