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 journalArticle

3 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

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Epithelial-Mesenchymal Transition
Glutamine
Glutaminase
Neoplasms
Small Interfering RNA
Cadherins
Fibronectins
Cultured Cells
pyruvate transport protein
Phenotype
Cell Line
Polymerase Chain Reaction
Enzymes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Takaoka, Y., Konno, M., Koseki, J., Colvin, H., Asai, A., Tamari, K., ... Ishii, H. (2019). Mitochondrial pyruvate carrier 1 expression controls cancer epithelial-mesenchymal transition and radioresistance. Cancer Science, 110(4), 1331-1339. https://doi.org/10.1111/cas.13980

Mitochondrial pyruvate carrier 1 expression controls cancer epithelial-mesenchymal transition and radioresistance. / Takaoka, Yuji; Konno, Masamitsu; Koseki, Jun; Colvin, Hugh; Asai, Ayumu; Tamari, Keisuke; Satoh, Taroh; Mori, Masaki; Doki, Yuichiro; Ogawa, Kazuhiko; Ishii, Hideshi.

In: Cancer Science, Vol. 110, No. 4, 04.2019, p. 1331-1339.

Research output: Contribution to journalArticle

Takaoka, Y, Konno, M, Koseki, J, Colvin, H, Asai, A, Tamari, K, Satoh, T, Mori, M, Doki, Y, Ogawa, K & Ishii, H 2019, 'Mitochondrial pyruvate carrier 1 expression controls cancer epithelial-mesenchymal transition and radioresistance', Cancer Science, vol. 110, no. 4, pp. 1331-1339. https://doi.org/10.1111/cas.13980
Takaoka, Yuji ; Konno, Masamitsu ; Koseki, Jun ; Colvin, Hugh ; Asai, Ayumu ; Tamari, Keisuke ; Satoh, Taroh ; Mori, Masaki ; Doki, Yuichiro ; Ogawa, Kazuhiko ; Ishii, Hideshi. / Mitochondrial pyruvate carrier 1 expression controls cancer epithelial-mesenchymal transition and radioresistance. In: Cancer Science. 2019 ; Vol. 110, No. 4. pp. 1331-1339.
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