Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress

Abstract Despite progress in the use of hyperthermia in clinical practice, the thermosensitivity of cancer cells is poorly understood. In a previous study, we found that sensitivity to hyperthermia varied between ovarian and uterine cancer cell lines. Upon hyperthermia, glycolytic enzymes decreased...

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Autores principales:	Taisei Kanamori, Natumi Miyazaki, Shigeki Aoki, Kousei Ito, Akihiro Hisaka, Hiroto Hatakeyama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29d450f437a043cead84a8f2f6f64499
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spelling	oai:doaj.org-article:29d450f437a043cead84a8f2f6f644992021-12-02T17:55:13ZInvestigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress10.1038/s41598-021-94031-92045-2322https://doaj.org/article/29d450f437a043cead84a8f2f6f644992021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94031-9https://doaj.org/toc/2045-2322Abstract Despite progress in the use of hyperthermia in clinical practice, the thermosensitivity of cancer cells is poorly understood. In a previous study, we found that sensitivity to hyperthermia varied between ovarian and uterine cancer cell lines. Upon hyperthermia, glycolytic enzymes decreased in hyperthermia-resistant SKOV3 cells. However, the mechanisms of glycolysis inhibition and their relationship with thermoresistance remain to be explored. In this study, metabolomic analysis indicated the downregulation of glycolytic metabolites in SKOV3 cells after hyperthermia. Proteomic and pathway analyses predicted that the ubiquitin pathway was explicitly activated in resistant SKOV3 cells, compared with hyperthermia-sensitive A2780 cells, and STUB1, a ubiquitin ligase, potentially targeted PKM, a glycolytic rate-limiting enzyme. PKM is degraded via ubiquitination upon hyperthermia. Although glycolysis is inactivated by hyperthermia, ATP production is maintained. We observed that oxygen consumption and mitochondrial membrane potential were activated in SKOV3 cells but suppressed in A2780 cells. The activation of mitochondria could compensate for the loss of ATP production due to the suppression of glycolysis by hyperthermia. Although the physiological significance has not yet been elucidated, our results demonstrated that metabolomic adaptation from the Warburg effect to mitochondrial oxidative phosphorylation could contribute to thermoresistance in ovarian and uterine cancer cells.Taisei KanamoriNatumi MiyazakiShigeki AokiKousei ItoAkihiro HisakaHiroto HatakeyamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Taisei Kanamori Natumi Miyazaki Shigeki Aoki Kousei Ito Akihiro Hisaka Hiroto Hatakeyama Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress
description	Abstract Despite progress in the use of hyperthermia in clinical practice, the thermosensitivity of cancer cells is poorly understood. In a previous study, we found that sensitivity to hyperthermia varied between ovarian and uterine cancer cell lines. Upon hyperthermia, glycolytic enzymes decreased in hyperthermia-resistant SKOV3 cells. However, the mechanisms of glycolysis inhibition and their relationship with thermoresistance remain to be explored. In this study, metabolomic analysis indicated the downregulation of glycolytic metabolites in SKOV3 cells after hyperthermia. Proteomic and pathway analyses predicted that the ubiquitin pathway was explicitly activated in resistant SKOV3 cells, compared with hyperthermia-sensitive A2780 cells, and STUB1, a ubiquitin ligase, potentially targeted PKM, a glycolytic rate-limiting enzyme. PKM is degraded via ubiquitination upon hyperthermia. Although glycolysis is inactivated by hyperthermia, ATP production is maintained. We observed that oxygen consumption and mitochondrial membrane potential were activated in SKOV3 cells but suppressed in A2780 cells. The activation of mitochondria could compensate for the loss of ATP production due to the suppression of glycolysis by hyperthermia. Although the physiological significance has not yet been elucidated, our results demonstrated that metabolomic adaptation from the Warburg effect to mitochondrial oxidative phosphorylation could contribute to thermoresistance in ovarian and uterine cancer cells.
format	article
author	Taisei Kanamori Natumi Miyazaki Shigeki Aoki Kousei Ito Akihiro Hisaka Hiroto Hatakeyama
author_facet	Taisei Kanamori Natumi Miyazaki Shigeki Aoki Kousei Ito Akihiro Hisaka Hiroto Hatakeyama
author_sort	Taisei Kanamori
title	Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress
title_short	Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress
title_full	Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress
title_fullStr	Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress
title_full_unstemmed	Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress
title_sort	investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/29d450f437a043cead84a8f2f6f64499
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Investigation of energy metabolic dynamism in hyperthermia-resistant ovarian and uterine cancer cells under heat stress

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