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Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma
Hürthle cell carcinoma (HCC) is a recurrent subtype of non-medullary thyroid cancer. HCC is characterized by profound whole-chromosome instability (w-CIN), resulting in a near-homozygous genome (NHG), a phenomenon recently attributed to reactive oxygen species (ROS) generated during mitosis by malfu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293353/ https://www.ncbi.nlm.nih.gov/pubmed/32533088 http://dx.doi.org/10.1038/s41598-020-66599-1 |
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author | Addie, Ruben D. Kostidis, Sarantos Corver, Willem E. Oosting, Jan Aminzadeh-Gohari, Sepideh Feichtinger, René G. Kofler, Barbara Aydemirli, Mehtap Derya Giera, Martin Morreau, Hans |
author_facet | Addie, Ruben D. Kostidis, Sarantos Corver, Willem E. Oosting, Jan Aminzadeh-Gohari, Sepideh Feichtinger, René G. Kofler, Barbara Aydemirli, Mehtap Derya Giera, Martin Morreau, Hans |
author_sort | Addie, Ruben D. |
collection | PubMed |
description | Hürthle cell carcinoma (HCC) is a recurrent subtype of non-medullary thyroid cancer. HCC is characterized by profound whole-chromosome instability (w-CIN), resulting in a near-homozygous genome (NHG), a phenomenon recently attributed to reactive oxygen species (ROS) generated during mitosis by malfunctioning mitochondria. We studied shared metabolic traits during standard and glucose-depleted cell culture in thyroid cancer cell lines (TCCLs), with or without a NHG, using quantitative analysis of extra and intracellular metabolites and ROS production following inhibition of complex III with antimycin A. We found that the XTC.UC1 and FTC-236 cell lines (both NHG) are functionally impaired in complex I and produce significantly more superoxide radicals than SW579 and BHP 2–7 (non-NHG) after challenge with antimycin A. FTC-236 showed the lowest levels of glutathione and SOD2. XTC.UC1 and FTC-236 both exhibited reduced glycolytic activity and utilization of alternative sources to meet energy demands. Both cell lines also shared low levels of α-ketoglutarate and high levels of creatine, phosphocreatine, uridine diphosphate-N-acetylglucosamine, pyruvate and acetylcarnitine. Furthermore, the metabolism of XTC.UC1 was skewed towards the de novo synthesis of aspartate, an effect that persisted even in glucose-free media, pointing to reductive carboxylation. Our data suggests that metabolic reprogramming and a subtle balance between ROS generation and scavenging/conversion of intermediates may be involved in ROS-induced w-CIN in HCC and possibly also in rare cases of follicular thyroid cancer showing a NHG. |
format | Online Article Text |
id | pubmed-7293353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72933532020-06-17 Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma Addie, Ruben D. Kostidis, Sarantos Corver, Willem E. Oosting, Jan Aminzadeh-Gohari, Sepideh Feichtinger, René G. Kofler, Barbara Aydemirli, Mehtap Derya Giera, Martin Morreau, Hans Sci Rep Article Hürthle cell carcinoma (HCC) is a recurrent subtype of non-medullary thyroid cancer. HCC is characterized by profound whole-chromosome instability (w-CIN), resulting in a near-homozygous genome (NHG), a phenomenon recently attributed to reactive oxygen species (ROS) generated during mitosis by malfunctioning mitochondria. We studied shared metabolic traits during standard and glucose-depleted cell culture in thyroid cancer cell lines (TCCLs), with or without a NHG, using quantitative analysis of extra and intracellular metabolites and ROS production following inhibition of complex III with antimycin A. We found that the XTC.UC1 and FTC-236 cell lines (both NHG) are functionally impaired in complex I and produce significantly more superoxide radicals than SW579 and BHP 2–7 (non-NHG) after challenge with antimycin A. FTC-236 showed the lowest levels of glutathione and SOD2. XTC.UC1 and FTC-236 both exhibited reduced glycolytic activity and utilization of alternative sources to meet energy demands. Both cell lines also shared low levels of α-ketoglutarate and high levels of creatine, phosphocreatine, uridine diphosphate-N-acetylglucosamine, pyruvate and acetylcarnitine. Furthermore, the metabolism of XTC.UC1 was skewed towards the de novo synthesis of aspartate, an effect that persisted even in glucose-free media, pointing to reductive carboxylation. Our data suggests that metabolic reprogramming and a subtle balance between ROS generation and scavenging/conversion of intermediates may be involved in ROS-induced w-CIN in HCC and possibly also in rare cases of follicular thyroid cancer showing a NHG. Nature Publishing Group UK 2020-06-12 /pmc/articles/PMC7293353/ /pubmed/32533088 http://dx.doi.org/10.1038/s41598-020-66599-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Addie, Ruben D. Kostidis, Sarantos Corver, Willem E. Oosting, Jan Aminzadeh-Gohari, Sepideh Feichtinger, René G. Kofler, Barbara Aydemirli, Mehtap Derya Giera, Martin Morreau, Hans Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma |
title | Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma |
title_full | Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma |
title_fullStr | Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma |
title_full_unstemmed | Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma |
title_short | Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma |
title_sort | metabolic reprogramming related to whole-chromosome instability in models for hürthle cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293353/ https://www.ncbi.nlm.nih.gov/pubmed/32533088 http://dx.doi.org/10.1038/s41598-020-66599-1 |
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