Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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
_version_ 1782515466338566144
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
work_keys_str_mv AT zhongyali pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT lixiaoli pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT jiyasai pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT lixiaoran pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT liyaqing pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT yudandan pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT yuanyuan pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT liujian pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT lihuixiang pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT zhangmingzhi pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT jizhenyu pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT fandandan pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT wenjianguo pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT goscinskimariuszadam pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT yuanlong pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT haobin pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT neslandjahnm pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers
AT suozhenhe pyruvatedehydrogenaseexpressionisnegativelyassociatedwithcellstemnessandworseclinicaloutcomeinprostatecancers