Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma

Abstract 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...

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Autores principales:	Ruben D. Addie, Sarantos Kostidis, Willem E. Corver, Jan Oosting, Sepideh Aminzadeh-Gohari, René G. Feichtinger, Barbara Kofler, Mehtap Derya Aydemirli, Martin Giera, Hans Morreau
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2ce5b5ec0ddc4e219631f5e1d5864d47
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spelling	oai:doaj.org-article:2ce5b5ec0ddc4e219631f5e1d5864d472021-12-02T17:52:23ZMetabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma10.1038/s41598-020-66599-12045-2322https://doaj.org/article/2ce5b5ec0ddc4e219631f5e1d5864d472020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-66599-1https://doaj.org/toc/2045-2322Abstract 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.Ruben D. AddieSarantos KostidisWillem E. CorverJan OostingSepideh Aminzadeh-GohariRené G. FeichtingerBarbara KoflerMehtap Derya AydemirliMartin GieraHans MorreauNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ruben D. Addie Sarantos Kostidis Willem E. Corver Jan Oosting Sepideh Aminzadeh-Gohari René G. Feichtinger Barbara Kofler Mehtap Derya Aydemirli Martin Giera Hans Morreau Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma
description	Abstract 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	article
author	Ruben D. Addie Sarantos Kostidis Willem E. Corver Jan Oosting Sepideh Aminzadeh-Gohari René G. Feichtinger Barbara Kofler Mehtap Derya Aydemirli Martin Giera Hans Morreau
author_facet	Ruben D. Addie Sarantos Kostidis Willem E. Corver Jan Oosting Sepideh Aminzadeh-Gohari René G. Feichtinger Barbara Kofler Mehtap Derya Aydemirli Martin Giera Hans Morreau
author_sort	Ruben D. Addie
title	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_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_sort	metabolic reprogramming related to whole-chromosome instability in models for hürthle cell carcinoma
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/2ce5b5ec0ddc4e219631f5e1d5864d47
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Metabolic reprogramming related to whole-chromosome instability in models for Hürthle cell carcinoma

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