Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.

Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic...

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Autores principales: Delphine Mirebeau-Prunier, Soazig Le Pennec, Caroline Jacques, Jean-Fred Fontaine, Naig Gueguen, Nathalie Boutet-Bouzamondo, Audrey Donnart, Yves Malthièry, Frédérique Savagner
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/53a2b26cfc1a405c842e10c235e3de98
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spelling oai:doaj.org-article:53a2b26cfc1a405c842e10c235e3de982021-11-18T07:53:35ZEstrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.1932-620310.1371/journal.pone.0058683https://doaj.org/article/53a2b26cfc1a405c842e10c235e3de982013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516535/?tool=EBIhttps://doaj.org/toc/1932-6203Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis.Delphine Mirebeau-PrunierSoazig Le PennecCaroline JacquesJean-Fred FontaineNaig GueguenNathalie Boutet-BouzamondoAudrey DonnartYves MalthièryFrédérique SavagnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58683 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Delphine Mirebeau-Prunier
Soazig Le Pennec
Caroline Jacques
Jean-Fred Fontaine
Naig Gueguen
Nathalie Boutet-Bouzamondo
Audrey Donnart
Yves Malthièry
Frédérique Savagner
Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.
description Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis.
format article
author Delphine Mirebeau-Prunier
Soazig Le Pennec
Caroline Jacques
Jean-Fred Fontaine
Naig Gueguen
Nathalie Boutet-Bouzamondo
Audrey Donnart
Yves Malthièry
Frédérique Savagner
author_facet Delphine Mirebeau-Prunier
Soazig Le Pennec
Caroline Jacques
Jean-Fred Fontaine
Naig Gueguen
Nathalie Boutet-Bouzamondo
Audrey Donnart
Yves Malthièry
Frédérique Savagner
author_sort Delphine Mirebeau-Prunier
title Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.
title_short Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.
title_full Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.
title_fullStr Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.
title_full_unstemmed Estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.
title_sort estrogen-related receptor alpha modulates lactate dehydrogenase activity in thyroid tumors.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/53a2b26cfc1a405c842e10c235e3de98
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