Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.

Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. To elucidate molecular mechanism(s) associated with IDH1/2 mutations, we established mouse embryonic fibroblasts (MEF) cells and hu...

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Autores principales:	Xun Liu, Kiyoshi Yamaguchi, Kiyoko Takane, Chi Zhu, Makoto Hirata, Yoko Hikiba, Shin Maeda, Yoichi Furukawa, Tsuneo Ikenoue
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/031a6d9977be47298caee411f152fdb2
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spelling	oai:doaj.org-article:031a6d9977be47298caee411f152fdb22021-12-02T20:08:18ZCancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.1932-620310.1371/journal.pone.0257090https://doaj.org/article/031a6d9977be47298caee411f152fdb22021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257090https://doaj.org/toc/1932-6203Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. To elucidate molecular mechanism(s) associated with IDH1/2 mutations, we established mouse embryonic fibroblasts (MEF) cells and human colorectal cancer cells stably expressing cancer-associated IDH1R132C or IDH2R172S, and analyzed the change in metabolic characteristics of the these cells. We found that IDH1/2 mutants induced intracellular 2-HG accumulation and inhibited cell proliferation. Expression profile analysis by RNA-seq unveiled that glucose transporter 1 (Glut1) was induced by the IDH1/2 mutants or treatment with 2-HG in the MEF cells. Consistently, glucose uptake and lactate production were increased by the mutants, suggesting the deregulation of glucose metabolism. Furthermore, PI3K/Akt/mTOR pathway and Hif1α expression were involved in the up-regulation of Glut1. Together, these results suggest that Glut1 is a potential target regulated by cancer-associated IDH1/2 mutations.Xun LiuKiyoshi YamaguchiKiyoko TakaneChi ZhuMakoto HirataYoko HikibaShin MaedaYoichi FurukawaTsuneo IkenouePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257090 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xun Liu Kiyoshi Yamaguchi Kiyoko Takane Chi Zhu Makoto Hirata Yoko Hikiba Shin Maeda Yoichi Furukawa Tsuneo Ikenoue Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.
description	Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. To elucidate molecular mechanism(s) associated with IDH1/2 mutations, we established mouse embryonic fibroblasts (MEF) cells and human colorectal cancer cells stably expressing cancer-associated IDH1R132C or IDH2R172S, and analyzed the change in metabolic characteristics of the these cells. We found that IDH1/2 mutants induced intracellular 2-HG accumulation and inhibited cell proliferation. Expression profile analysis by RNA-seq unveiled that glucose transporter 1 (Glut1) was induced by the IDH1/2 mutants or treatment with 2-HG in the MEF cells. Consistently, glucose uptake and lactate production were increased by the mutants, suggesting the deregulation of glucose metabolism. Furthermore, PI3K/Akt/mTOR pathway and Hif1α expression were involved in the up-regulation of Glut1. Together, these results suggest that Glut1 is a potential target regulated by cancer-associated IDH1/2 mutations.
format	article
author	Xun Liu Kiyoshi Yamaguchi Kiyoko Takane Chi Zhu Makoto Hirata Yoko Hikiba Shin Maeda Yoichi Furukawa Tsuneo Ikenoue
author_facet	Xun Liu Kiyoshi Yamaguchi Kiyoko Takane Chi Zhu Makoto Hirata Yoko Hikiba Shin Maeda Yoichi Furukawa Tsuneo Ikenoue
author_sort	Xun Liu
title	Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.
title_short	Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.
title_full	Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.
title_fullStr	Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.
title_full_unstemmed	Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.
title_sort	cancer-associated idh mutations induce glut1 expression and glucose metabolic disorders through a pi3k/akt/mtorc1-hif1α axis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/031a6d9977be47298caee411f152fdb2
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Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.

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