ArticlePloS one2017
IDH1 R132H Mutation Enhances Cell Migration by Activating AKT-mTOR Signaling Pathway, but Sensitizes Cells to 5-FU Treatment as NADPH and GSH Are Reduced.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 3 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 3 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Melanoma of unknown primary: a comprehensive review of immune-mediated pathogenesis and therapies.The oncologist · 2025Pooled it
- Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Older studies can underestimate prognosis of glioblastoma biomarker in meta-analyses: a meta-epidemiological study for study-level effect in the current literature.Journal of neuro-oncology · 2018Pooled it
- The effects of BMP2 and the mechanisms involved in the invasion and angiogenesis of IDH1 mutant glioma cells.Journal of neuro-oncology · 2024Article
- IDH1 mutation activates mTOR signaling pathway, promotes cell proliferation and invasion in glioma cells.Molecular biology reports · 2022Article
- Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model.International journal of molecular sciences · 2022Article
- A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database.Cancers · 2021Article
- Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study.Clinical breast cancer · 2021Article
- Proteins moonlighting in tumor metabolism and epigenetics.Frontiers of medicine · 2021Review
- Evaluating Mechanisms of IDH1 Regulation through Site-Specific Acetylation Mimics.Biomolecules · 2021Article
- A Review of Multiple Venous Malformations of the Upper Limb: Classification, Genetics, and Pathogenesis.Plastic and reconstructive surgery. Global open · 2021Article
- Current biomarker-associated procedures of cancer modeling-a reference in the context of IDH1 mutant glioma.Cell death & disease · 2020Review
- Wild‑type IDH1 affects cell migration by modulating the PI3K/AKT/mTOR pathway in primary glioblastoma cells.Molecular medicine reports · 2020Article
- Specific patterns of H3K79 methylation influence genetic interaction of oncogenes in AML.Blood advances · 2020Article
- Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML.Blood advances · 2020Article
- Mitochondria in cancer.Cell stress · 2020Review
- Review
- Molecular Subgroups of Glioblastoma- an Assessment by Immunohistochemical Markers.Pathology oncology research : POR · 2019Article
- Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC.Neuro-oncology · 2018Article
- Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma.Blood · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aim of studyMutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) gene were recently discovered in vast majority of World Health Organization (WHO) grade II/III gliomas. This study is to understand the effects of IDH1 R132H mutation in gliomagenesis and to develop new strategies to treat glioma with IDH1 R132H mutation. MATERIALS AND
methodsOver expression of IDH1 R132H in U87MG cells was done by transfecting cells with IDH1 R132H plasmid. MTT assay, scratch repair assay and western blot were performed to study effects of IDH1 R132H mutation on cell proliferation, migration, regulating AKT-mTOR signaling pathway and cell death respectively. NADP+/NADPH and GSH quantification assays were performed to evaluate effects of IDH1 R132H mutation on the production of antioxidant NADPH and GSH.
resultsWe found that over expression of IDH1 R132H mutation decreased cell proliferation consistent with previous reports; however, it increased cell migration and enhanced AKT-mTOR signaling pathway activation. Mutations in isocitrate dehydrogenase (IDH) 1 also change the function of the enzymes and cause them to produce 2-hydroxyglutarate and not produce NADPH. We tested the level of NADPH and GSH and demonstrated that IDH1 R132H mutant stable cells had significantly low NADPH and GSH level compared to control or IDH1 wild type stable cells. The reduced antioxidants (NADPH and GSH) sensitized U87MG cells with IDH R132H mutant to 5-FU treatment.
conclusionOur study highlights the important role of IHD1 R132H mutant in up- regulating AKT-mTOR signaling pathway and enhancing cell migration. Furthermore, we demonstrate that IDH1 R132H mutation affects cellular redox status and sensitizes gliomas cells with IDH1 R132H mutation to 5FU treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.