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Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis
by
Yamaguchi, Kiyoshi
, Maeda, Shin
, Hirata, Makoto
, Hikiba, Yoko
, Furukawa, Yoichi
, Ikenoue, Tsuneo
, Zhu, Chi
, Takane, Kiyoko
, Liu, Xun
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Animals
/ Biology and Life Sciences
/ Cancer
/ Cell Proliferation
/ Colorectal cancer
/ Colorectal carcinoma
/ Deregulation
/ Embryo fibroblasts
/ Enzymes
/ Experiments
/ Fibroblasts
/ Fibroblasts - metabolism
/ Gastroenterology
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Glucose
/ Glucose - metabolism
/ Glucose Metabolism Disorders - genetics
/ Glucose transporter
/ Glucose Transporter Type 1 - metabolism
/ Glutarates - metabolism
/ Glycolysis
/ HCT116 Cells
/ Humans
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Intracellular Space - metabolism
/ Isocitrate dehydrogenase
/ Isocitrate Dehydrogenase - genetics
/ Kinases
/ Laboratory animals
/ Lactic acid
/ Lactic Acid - metabolism
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Medicine
/ Medicine and Health Sciences
/ Metabolic disorders
/ Metabolism
/ Metabolites
/ Mice
/ Mice, Inbred C57BL
/ Mutant Proteins - metabolism
/ Mutants
/ Mutation
/ Mutation - genetics
/ Neoplasms - genetics
/ Phosphatidylinositol 3-Kinases - metabolism
/ Physical Sciences
/ Plasmids
/ Proteins
/ Proto-Oncogene Proteins c-akt - metabolism
/ Signal Transduction
/ TOR protein
/ Tumorigenesis
2021
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Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis
by
Yamaguchi, Kiyoshi
, Maeda, Shin
, Hirata, Makoto
, Hikiba, Yoko
, Furukawa, Yoichi
, Ikenoue, Tsuneo
, Zhu, Chi
, Takane, Kiyoko
, Liu, Xun
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Animals
/ Biology and Life Sciences
/ Cancer
/ Cell Proliferation
/ Colorectal cancer
/ Colorectal carcinoma
/ Deregulation
/ Embryo fibroblasts
/ Enzymes
/ Experiments
/ Fibroblasts
/ Fibroblasts - metabolism
/ Gastroenterology
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Glucose
/ Glucose - metabolism
/ Glucose Metabolism Disorders - genetics
/ Glucose transporter
/ Glucose Transporter Type 1 - metabolism
/ Glutarates - metabolism
/ Glycolysis
/ HCT116 Cells
/ Humans
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Intracellular Space - metabolism
/ Isocitrate dehydrogenase
/ Isocitrate Dehydrogenase - genetics
/ Kinases
/ Laboratory animals
/ Lactic acid
/ Lactic Acid - metabolism
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Medicine
/ Medicine and Health Sciences
/ Metabolic disorders
/ Metabolism
/ Metabolites
/ Mice
/ Mice, Inbred C57BL
/ Mutant Proteins - metabolism
/ Mutants
/ Mutation
/ Mutation - genetics
/ Neoplasms - genetics
/ Phosphatidylinositol 3-Kinases - metabolism
/ Physical Sciences
/ Plasmids
/ Proteins
/ Proto-Oncogene Proteins c-akt - metabolism
/ Signal Transduction
/ TOR protein
/ Tumorigenesis
2021
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Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis
by
Yamaguchi, Kiyoshi
, Maeda, Shin
, Hirata, Makoto
, Hikiba, Yoko
, Furukawa, Yoichi
, Ikenoue, Tsuneo
, Zhu, Chi
, Takane, Kiyoko
, Liu, Xun
in
1-Phosphatidylinositol 3-kinase
/ AKT protein
/ Animals
/ Biology and Life Sciences
/ Cancer
/ Cell Proliferation
/ Colorectal cancer
/ Colorectal carcinoma
/ Deregulation
/ Embryo fibroblasts
/ Enzymes
/ Experiments
/ Fibroblasts
/ Fibroblasts - metabolism
/ Gastroenterology
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Glucose
/ Glucose - metabolism
/ Glucose Metabolism Disorders - genetics
/ Glucose transporter
/ Glucose Transporter Type 1 - metabolism
/ Glutarates - metabolism
/ Glycolysis
/ HCT116 Cells
/ Humans
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Intracellular Space - metabolism
/ Isocitrate dehydrogenase
/ Isocitrate Dehydrogenase - genetics
/ Kinases
/ Laboratory animals
/ Lactic acid
/ Lactic Acid - metabolism
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Medicine
/ Medicine and Health Sciences
/ Metabolic disorders
/ Metabolism
/ Metabolites
/ Mice
/ Mice, Inbred C57BL
/ Mutant Proteins - metabolism
/ Mutants
/ Mutation
/ Mutation - genetics
/ Neoplasms - genetics
/ Phosphatidylinositol 3-Kinases - metabolism
/ Physical Sciences
/ Plasmids
/ Proteins
/ Proto-Oncogene Proteins c-akt - metabolism
/ Signal Transduction
/ TOR protein
/ Tumorigenesis
2021
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Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis
Journal Article
Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis
2021
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Overview
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 IDH1 R132C or IDH2 R172S , 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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
1-Phosphatidylinositol 3-kinase
/ Animals
/ Cancer
/ Enzymes
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Glucose
/ Glucose Metabolism Disorders - genetics
/ Glucose Transporter Type 1 - metabolism
/ Humans
/ Hypoxia-Inducible Factor 1, alpha Subunit
/ Intracellular Space - metabolism
/ Isocitrate Dehydrogenase - genetics
/ Kinases
/ Mechanistic Target of Rapamycin Complex 1 - metabolism
/ Medicine
/ Medicine and Health Sciences
/ Mice
/ Mutant Proteins - metabolism
/ Mutants
/ Mutation
/ Phosphatidylinositol 3-Kinases - metabolism
/ Plasmids
/ Proteins
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