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

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....

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Autores principales: Takaoka, Yuji, Konno, Masamitsu, Koseki, Jun, Colvin, Hugh, Asai, Ayumu, Tamari, Keisuke, Satoh, Taroh, Mori, Masaki, Doki, Yuichiro, Ogawa, Kazuhiko, Ishii, Hideshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447954/
https://www.ncbi.nlm.nih.gov/pubmed/30801869
http://dx.doi.org/10.1111/cas.13980
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author Takaoka, Yuji
Konno, Masamitsu
Koseki, Jun
Colvin, Hugh
Asai, Ayumu
Tamari, Keisuke
Satoh, Taroh
Mori, Masaki
Doki, Yuichiro
Ogawa, Kazuhiko
Ishii, Hideshi
author_facet Takaoka, Yuji
Konno, Masamitsu
Koseki, Jun
Colvin, Hugh
Asai, Ayumu
Tamari, Keisuke
Satoh, Taroh
Mori, Masaki
Doki, Yuichiro
Ogawa, Kazuhiko
Ishii, Hideshi
author_sort Takaoka, Yuji
collection PubMed
description 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.
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spelling pubmed-64479542019-04-15 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 Cancer Sci Original Articles 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. John Wiley and Sons Inc. 2019-04-04 2019-04 /pmc/articles/PMC6447954/ /pubmed/30801869 http://dx.doi.org/10.1111/cas.13980 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
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
title Mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance
title_full Mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance
title_fullStr Mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance
title_full_unstemmed Mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance
title_short Mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance
title_sort mitochondrial pyruvate carrier 1 expression controls cancer epithelial‐mesenchymal transition and radioresistance
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447954/
https://www.ncbi.nlm.nih.gov/pubmed/30801869
http://dx.doi.org/10.1111/cas.13980
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