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

Yuji Takaoka, Masamitsu Konno, Jun Koseki, Hugh Colvin, Ayumu Asai, Keisuke Tamari, Taroh Satoh, Masaki Mori, Yuichiro Doki, Kazuhiko Ogawa, Hideshi Ishii

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1331-1339
Number of pages9
JournalCancer Science
Volume110
Issue number4
DOIs
Publication statusPublished - Apr 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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