ArticleNeuro-oncology2015
Activation of the NRF2 pathway and its impact on the prognosis of anaplastic glioma patients.
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Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36citing papers in PubMed
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Targeting metabolic mechanisms to overcome temozolomide resistance in glioblastoma.Discover oncology · 2026Review
- Effects of the Pharmacological Modulation of NRF2 in Cancer Progression.Medicina (Kaunas, Lithuania) · 2025Review
- State-of-the-art photodynamic therapy for malignant gliomas: innovations in photosensitizers and combined therapeutic approaches.Exploration of targeted anti-tumor therapy · 2025Review
- Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management.Cell communication and signaling : CCS · 2024Review
- KEAP1-mutant atypical meningioma: illustrative case.Journal of neurosurgery. Case lessons · 2024Article
- interFLOW: maximum flow framework for the identification of factors mediating the signaling convergence of multiple receptors.NPJ systems biology and applications · 2024Article
- Glutathione metabolism-related gene signature predicts prognosis and treatment response in low-grade glioma.Aging · 2024Article
- The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases.Biomedicines · 2023Review
- Exploring the role of Nrf2 signaling in glioblastoma multiforme.Discover oncology · 2022Review
- Normal and Pathological NRF2 Signalling in the Central Nervous System.Antioxidants (Basel, Switzerland) · 2022Review
- The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications.Medical oncology (Northwood, London, England) · 2022Review
- Hippo Pathway in Regulating Drug Resistance of Glioblastoma.International journal of molecular sciences · 2021Review
- Review
- PSMD12 promotes glioma progression by upregulating the expression of Nrf2.Annals of translational medicine · 2021Article
- Enhancer remodeling promotes tumor-initiating activity in NRF2-activated non-small cell lung cancers.Nature communications · 2020Article
- WIP Modulates Oxidative Stress through NRF2/KEAP1 in Glioblastoma Cells.Antioxidants (Basel, Switzerland) · 2020Article
- Metabolic features of cancer cells in NRF2 addiction status.Biophysical reviews · 2020Review
- Transcription factor NRF2 uses the Hippo pathway effector TAZ to induce tumorigenesis in glioblastomas.Redox biology · 2020Article
- Open Data for Differential Network Analysis in Glioma.International journal of molecular sciences · 2020Article
- An Autophagy-Related Gene Signature Associated With Clinical Prognosis and Immune Microenvironment in Gliomas.Frontiers in oncology · 2020Article
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Authors and funding
17 authors at 4 institutions in 1 country.
Masayuki KanamoriDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Tsuyoshi HigaDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Yukihiko SonodaDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Shohei MurakamiDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Mina DodoDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Hiroshi KitamuraDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Keiko TaguchiDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Tatsuhiro ShibataDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Mika WatanabeDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Hiroyoshi SuzukiDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Ichiyo ShibaharaDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Ryuta SaitoDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Yoji YamashitaDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Toshihiro KumabeDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Masayuki YamamotoDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Hozumi MotohashiDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Teiji TominagaDepartment of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (M.K., Y.S., I.S., R.S., T.K., T.T.); Department of Gene Expression Regulation, Institute of Development, Aging, and Cancer, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H., S.M., M.D., H.K., K.T., H.M.); Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (T.H.); Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan (S.M., K.T., M.Y.); Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan (T.S.); Department of Pathology, Tohoku University Hospital, Sendai, Miyagi, Japan (M.W.); Department of Pathology and Laboratory Medicine, Sendai Medical Center, Sendai, Miyagi, Japan (H.S.); Department of Neurosurgery, Miyagi Cancer Center, Natori, Miyagi, Japan (Y.Y.).
Sendai Medical Center · JPTohoku University Hospital · JPMiyagi Prefectural Hospital Organization · JPTohoku University · JP
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNuclear factor erythroid 2-related factor 2 (NRF2) plays pivotal roles in cytoprotection. We aimed at clarifying the contribution of the NRF2 pathway to malignant glioma pathology.
methodsNRF2 target gene expression and its association with prognosis were examined in 95 anaplastic gliomas with or without isocitrate dehydrogenase (IDH) 1/2 gene mutations and 52 glioblastomas. To explore mechanisms for the altered activity of the NRF2 pathway, we examined somatic mutations and expressions of the NRF2 gene and those encoding NRF2 regulators, Kelch-like ECH-associated protein 1 (KEAP1) and p62/SQSTSM. To clarify the functional interaction between IDH1 mutations and the NRF2 pathway, we introduced a mutant IDH1 to T98 glioblastoma-derived cells and examined the NRF2 activity in these cells.
resultsNRF2 target genes were elevated in 13.7% and 32.7% of anaplastic gliomas and glioblastomas, respectively. Upregulation of NRF2 target genes correlated with poor prognosis in anaplastic gliomas but not in glioblastomas. Neither somatic mutations of NRF2/KEAP1 nor dysregulated expression of KEAP1/p62 explained the increased expression of NRF2 target genes. In most cases of anaplastic glioma with mutated IDH1/2, NRF2 and its target genes were downregulated. This was reproducible in IDH1 R132H-expressing T98 cells. In minor cases of IDH1/2-mutant anaplastic gliomas with increased expression of NRF2 target genes, the clinical outcomes were significantly poor.
conclusionsThe NRF2 activity is increased in a significant proportion of malignant gliomas in general but decreased in the majority of IDH1/2-mutant anaplastic gliomas. It is plausible that the NRF2 pathway plays an important role in tumor progression of anaplastic gliomas with IDH1/2 mutations.
Indexed as
Signal TransductionAdolescentAdultAgedAged, 80 and overBrain NeoplasmsChildFemaleGene ExpressionGlioblastomaGliomaHumansIntracellular Signaling Peptides and ProteinsIsocitrate DehydrogenaseKelch-Like ECH-Associated Protein 1MaleIDH1 protein, humanIDH2 protein, humanIntracellular Signaling Peptides and ProteinsIsocitrate DehydrogenaseKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2P62 protein, humanRNA-Binding ProteinsIDH1/2 geneKeap1-NRF2 systemmalignant gliomaprognosis
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