Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis
| Autor: | Kiyoko Takane, Yoko Hikiba, Chi Zhu, Yoichi Furukawa, Kiyoshi Yamaguchi, Makoto Hirata, Shin Maeda, Tsuneo Ikenoue, Xun Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Metabolic Processes
Carcinogenesis Glucose uptake Intracellular Space mTORC1 medicine.disease_cause Biochemistry Phosphatidylinositol 3-Kinases Glucose Metabolism Neoplasms Medicine and Health Sciences Glucose Transporter Type 1 Multidisciplinary biology Chemistry Organic Compounds Monosaccharides Small interfering RNA Isocitrate Dehydrogenase Nucleic acids Gene Expression Regulation Neoplastic Isocitrate dehydrogenase Oncology Cell Processes Physical Sciences Medicine Carbohydrate Metabolism Glycolysis Research Article Signal Transduction Science Carbohydrates Mechanistic Target of Rapamycin Complex 1 Glutarates medicine Genetics Animals Humans Lactic Acid Non-coding RNA Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Glucose Metabolism Disorders Colorectal Cancer Organic Chemistry Glucose transporter Chemical Compounds Biology and Life Sciences Cancers and Neoplasms Cell Biology Fibroblasts HCT116 Cells Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology Gene regulation Mice Inbred C57BL Metabolism Glucose Mutation biology.protein RNA GLUT1 Mutant Proteins Gene expression Proto-Oncogene Proteins c-akt |
| Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 9, p e0257090 (2021) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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