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Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers
Cells generate adenosine-5′-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the “Warburg Effect”, in which cancer cells...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355102/ https://www.ncbi.nlm.nih.gov/pubmed/28076853 http://dx.doi.org/10.18632/oncotarget.14527 |
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author | Zhong, Yali Li, Xiaoli Ji, Yasai Li, Xiaoran Li, Yaqing Yu, Dandan Yuan, Yuan Liu, Jian Li, Huixiang Zhang, Mingzhi Ji, Zhenyu Fan, Dandan Wen, Jianguo Goscinski, Mariusz Adam Yuan, Long Hao, Bin Nesland, Jahn M Suo, Zhenhe |
author_facet | Zhong, Yali Li, Xiaoli Ji, Yasai Li, Xiaoran Li, Yaqing Yu, Dandan Yuan, Yuan Liu, Jian Li, Huixiang Zhang, Mingzhi Ji, Zhenyu Fan, Dandan Wen, Jianguo Goscinski, Mariusz Adam Yuan, Long Hao, Bin Nesland, Jahn M Suo, Zhenhe |
author_sort | Zhong, Yali |
collection | PubMed |
description | Cells generate adenosine-5′-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the “Warburg Effect”, in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1). To further analyze the function of PDHA1 in cancer cells, it was knock out (KO) in the human prostate cancer cell line LnCap and a stable KO cell line was established. We demonstrated that PDHA1 gene KO significantly decreased mitochondrial OXPHOS and promoted anaerobic glycolysis, accompanied with higher stemness phenotype including resistance to chemotherapy, enhanced migration ability and increased expression of cancer stem cell markers. We also examined PDHA1 protein expression in prostate cancer tissues by immunohistochemistry and observed that reduced PDHA1 protein expression in clinical prostate carcinomas was significantly correlated with poor prognosis. Collectively, our results show that negative PDHA1 gene expressionis associated with significantly higher cell stemness in prostate cancer cells and reduced protein expression of this gene is associated with shorter clinical outcome in prostate cancers. |
format | Online Article Text |
id | pubmed-5355102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53551022017-04-15 Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers Zhong, Yali Li, Xiaoli Ji, Yasai Li, Xiaoran Li, Yaqing Yu, Dandan Yuan, Yuan Liu, Jian Li, Huixiang Zhang, Mingzhi Ji, Zhenyu Fan, Dandan Wen, Jianguo Goscinski, Mariusz Adam Yuan, Long Hao, Bin Nesland, Jahn M Suo, Zhenhe Oncotarget Research Paper Cells generate adenosine-5′-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the “Warburg Effect”, in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1). To further analyze the function of PDHA1 in cancer cells, it was knock out (KO) in the human prostate cancer cell line LnCap and a stable KO cell line was established. We demonstrated that PDHA1 gene KO significantly decreased mitochondrial OXPHOS and promoted anaerobic glycolysis, accompanied with higher stemness phenotype including resistance to chemotherapy, enhanced migration ability and increased expression of cancer stem cell markers. We also examined PDHA1 protein expression in prostate cancer tissues by immunohistochemistry and observed that reduced PDHA1 protein expression in clinical prostate carcinomas was significantly correlated with poor prognosis. Collectively, our results show that negative PDHA1 gene expressionis associated with significantly higher cell stemness in prostate cancer cells and reduced protein expression of this gene is associated with shorter clinical outcome in prostate cancers. Impact Journals LLC 2017-01-05 /pmc/articles/PMC5355102/ /pubmed/28076853 http://dx.doi.org/10.18632/oncotarget.14527 Text en Copyright: © 2017 Zhong et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhong, Yali Li, Xiaoli Ji, Yasai Li, Xiaoran Li, Yaqing Yu, Dandan Yuan, Yuan Liu, Jian Li, Huixiang Zhang, Mingzhi Ji, Zhenyu Fan, Dandan Wen, Jianguo Goscinski, Mariusz Adam Yuan, Long Hao, Bin Nesland, Jahn M Suo, Zhenhe Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers |
title | Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers |
title_full | Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers |
title_fullStr | Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers |
title_full_unstemmed | Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers |
title_short | Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers |
title_sort | pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355102/ https://www.ncbi.nlm.nih.gov/pubmed/28076853 http://dx.doi.org/10.18632/oncotarget.14527 |
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