Cited by 1,395Genomics, phytochemicals, and oxidative stressCancer, Hypoxia, and MetabolismMetabolism, Diabetes, and Cancer

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Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming

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Mitsuishi, Yoichiro, Taguchi, Keiko, Kawatani, Yukie, Shibata, Tatsuhiro, Nukiwa, Toshihiro, Aburatani, Hiroyuki, Yamamoto, Masayuki, Motohashi, Hozumi·2012·Cancer Cell

DOI 10.1016/j.ccr.2012.05.016

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Abstract

Cancer cells consume large quantities of nutrients and maintain high levels of anabolism. Recent studies revealed that various oncogenic pathways are involved in modulation of metabolism. Nrf2, a key regulator for the maintenance of redox homeostasis, has been shown to contribute to malignant phenotypes of cancers including aggressive proliferation. However, the mechanisms with which Nrf2 accelerates proliferation are not fully understood. Here, we show that Nrf2 redirects glucose and glutamine into anabolic pathways, especially under the sustained activation of PI3K-Akt signaling. The active PI3K-Akt pathway augments the nuclear accumulation of Nrf2 and enables Nrf2 to promote metabolic activities that support cell proliferation in addition to enhancing cytoprotection. The functional expansion of Nrf2 reinforces the metabolic reprogramming triggered by proliferative signals.

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Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244
PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088
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Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6943 · Cited by 3,999
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DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622
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Tumor cell metabolism: cancer's Achilles' heel
Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337
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Lu, S. C.-L. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.05.005 · Cited by 2,131
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Düvel, K., Yecies, J. L., Menon, S., Raman, P., Lipovsky, A. I., Souza, A. L., Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.06.022 · Cited by 2,020
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Background
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Background
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BackgroundSelf-citation
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Self-citation
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Background
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Background
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Background
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Background
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Background
A potential therapeutic strategy based on acute oxidative stress induction for wild-type NRF2/KEAP1 lung squamous cell carcinoma
Sánchez-Ortega, M., Garrido, A., Cirauqui, C., Sanz-Gonzalez, L., Hernández, M. C., González-Garcı́a, A., Obregon, K., Ferrer, I., Paz-Ares, L., & Carrera, A. C. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103305 · Cited by 14
Chemo-proteomics reveals dihydrocaffeic acid exhibits anti-inflammation effects via Transaldolase 1 mediated PERK-NF-κB pathway
Li, G., Li, H., Wang, P., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-024-01958-3 · Cited by 13
“It is reported that lacking of TALDO1 is related to various of clinical symptoms, including coagulopathy, liver dysfunction and tumor [33], and high levels of TALDO1 have been found in various tumors [34].”
Therapeutic efficacy of canagliflozin against hepatocarcinogenesis induced by CDD/DEN/TAA in a rat model: regulation of AMPK/HIF-1α/YAP-1/TAZ signaling pathways
Fayed, H. M., Asaad, G. F., Elbaset, M. A., Sharaf, O. A., Mahmoud, S. S., Amin, M. M., El‐Gendy, Z. A., Ibrahim, F. A., Abdelgayed, S. S., & Abdel-Rahman, R. F. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04098-8 · Cited by 13
“Furthermore, Nrf2 promotes intermediate metabolism by means of glutaminolysis (Romero et al. 2017), which leads to an imbalance in metabolic activities, including nucleotide (Mitsuishi et al. 2012) and amino acid biosynthesis (DeNicola et al. 2015).”
Pathophysiological Potentials of NRF3-Regulated Transcriptional Axes in Protein and Lipid Homeostasis
Waku, T., & Kobayashi, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312686 · Cited by 12
“NRF2 also activates genes encoding enzymes for glutaminolysis, shifting the metabolic flux of glutamine to the glutathione synthesis pathway [14,15].”
Background
Curcumenol Targeting YWHAG Inhibits the Pentose Phosphate Pathway and Enhances Antitumor Effects of Cisplatin
Mao, Z., Zhong, L., Zhuang, X., Liu, H., & Peng, Y. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/3988916 · Cited by 13
“*is metabolic change is a hallmark of cancer cells [41].”
Background
DNMT3A R882H mutation promotes acute leukemic cell survival by regulating glycolysis through the NRF2/NQO1 axis
Chu, X., Zhong, L., Dan, W., Wang, X., Zhang, Z., Liu, Z., Lu, Y., Shao, X., Zhou, Z., Chen, S., et al. (2023) · Cellular Signalling · doi:10.1016/j.cellsig.2023.110626 · Cited by 13
Increased Nrf2 expression by renal cell carcinoma is associated with postoperative chronic kidney disease and an unfavorable prognosis
Yuki, H., Kamai, T., Murakami, S., Higashi, S., Narimatsu, T., Kambara, T., Betsunoh, H., Abe, H., Arai, K., Shirataki, H., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.25322 · Cited by 13
“They also stated that activation of the PI3K-Akt pathway augments nuclear accumulation of Nrf2 and supports cell proliferation, as well as enhancing cytoprotection, indicating that Nrf2 activation promotes metabolic reprogramming triggered by proliferative signals [11].”
Background
Marine Peroxy Sesquiterpenoids Induce Apoptosis by Modulation of Nrf2-ARE Signaling in HCT116 Colon Cancer Cells
Taira, J., Miyazato, H., & Ueda, K. (2018) · Marine Drugs · doi:10.3390/md16100347 · Cited by 13
The discovery and characterization of K‐563, a novel inhibitor of the Keap1/Nrf2 pathway produced by Streptomyces sp
Hori, R., Yamaguchi, K., Sato, H., Watanabe, M., Tsutsumi, K., Iwamoto, S., Abe, M., Onodera, H., Nakamura, S., & Nakai, R. (2019) · Cancer Medicine · doi:10.1002/cam4.1949 · Cited by 13
Systematic Identification of Multi Omics-based Biomarkers in KEAP1 Mutated TCGA Lung Adenocarcinoma
Namani, A., Zheng, Z.-H., Wang, X. J., & Tang, X. (2019) · Journal of Cancer · doi:10.7150/jca.35489 · Cited by 13
“Seminal studies on NRF2 pathway revealed its specific role in metabolic reprogramming [9], carbon metabolism [10], serine biosynthesis [11] in Ivyspring”
Background
Genetic activation of Nrf2 reduces cutaneous symptoms in a murine model of Netherton syndrome
Muzumdar, S., Koch, M., Hiebert, H., Bapst, A. M., Gravina, A., Bloch, W., Beer, H., Werner, S., & Schäfer, M. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.042648 · Cited by 14
“A large number of additional Nrf2 target genes have been described; for example, genes involved in the unfolded protein response, in the formation of atherosclerotic plaques, in purine biosynthesis (Harada et al., 2012; Meakin et al., 2014; Mitsuishi et al., 2012; Rolfs et al., 2015; Tonelli et al., 2018) and in extra…”
Background
Are we still on the right path(way)?: the altered expression of the pentose phosphate pathway in solid tumors and the potential of its inhibition in combination therapy
Meskers, C. J. W., Frańczak, M., Smolenski, R. T., Giovannetti, E., & Peters, G. J. (2022) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2022.2049234 · Cited by 13
“Furthermore, oncogenic pathways such as EGFR-mediated signaling have been shown to increase activity of enzymes in the PPP [6], and G6PD, 6PGD, TKT, and TALDO can be upregulated by NRF-2 via PIK3/Akt-mediated signaling [4,13].”
Background
Nrf2 in Host Defense: Over the Rainbow
Cho, H., Kwak, M., & Pi, J. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/975839 · Cited by 13
Metabolic Phenotypes, Dependencies, and Adaptation in Lung CancerPreprint
DeNicola, G. M., & Shackelford, D. B. (2021) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a037838 · Cited by 13
Advances in targeting glycogen synthase kinase 3β for diabetes therapy
Wang, F., Li, Y., Bai, L., Xiao, W., Zhong, L., & Shi, J. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.109051 · Cited by 14
Nrf2 Drives Hepatocellular Carcinoma Progression through Acetyl-CoA–Mediated Metabolic and Epigenetic Regulatory Networks
Xi, C., Pang, J., Barrett, A., Horuzsko, A., Ande, S., Mivechi, N. F., & Zhu, X. (2023) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-22-0935 · Cited by 12
The regulation of amino acid metabolism in tumor cell death: from the perspective of physiological functions
Wang, J., Wang, H., Gao, M., Zhang, Y., Zhang, L., Huang, D., Tu, K., & Xu, Q. (2023) · APOPTOSIS · doi:10.1007/s10495-023-01875-9 · Cited by 14
“The synthesis of GSH involves two ATPdemanding steps: the formation of γ-glutamylcysteine from glutamate and cysteine, and the production of GSH from γ-glutamylcysteine and glycine [59].”
BackgroundInfluential
Metabolic barriers in non-small cell lung cancer with LKB1 and/or KEAP1 mutations for immunotherapeutic strategies
Tanaka, I., Koyama, J., Itoigawa, H., Hayai, S., & Morise, M. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1249237 · Cited by 13
“Activation of NRF2 signaling resulting from KEAP1 inactivation promotes glucose and Gln metabolism toward the anabolic pathway through phosphatidylinositol 3’-kinase/protein kinase B signaling (112).”
Background
Macrophages: plastic participants in the diagnosis and treatment of head and neck squamous cell carcinoma
Chen, L., Chu, Y., Ye, Z., Gu, S., Hu, Y., He, J., & Shen, Z. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1337129 · Cited by 13
The Role of NRF2 in Trinucleotide Repeat Expansion Disorders
Chang, K., & Chen, C. (2024) · Antioxidants · doi:10.3390/antiox13060649 · Cited by 12
Nicotinamide adenine dinucleotide phosphate alleviates intestinal ischemia/reperfusion injury via Nrf2/HO-1 pathway
Chen, S.-Y., Xu, H. Z., Qin, Y., He, T., Shi, R., Xing, Y.-R., Xu, J., Cong, R., Wang, M., Yang, J., et al. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113478 · Cited by 12
Arctiin alleviates knee osteoarthritis by suppressing chondrocyte oxidative stress induced by accumulated iron via AKT/NRF2/HO-1 signaling pathway
Yang, J., Chen, D., He, Q., Chen, B., Pan, Z., Zhang, G., Li, M., Li, S., Xiao, J., Wang, H., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-83383-7 · Cited by 12
The Central Role of NRF2 in Cancer Metabolism and Redox Signaling: Novel Insights into Crosstalk with ER Stress and Therapeutic Modulation
Joof, A. N., Bajinka, O., Zhou, Y., Ren, F., & Tan, Y. (2025) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-025-01821-3 · Cited by 16
HPD overexpression predicts poor prognosis in breast cancer
Wang, X., Shang, Y., Yang, L., et al. (2019) · Pathology - Research and Practice · doi:10.1016/j.prp.2019.152524 · Cited by 12
Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) in autophagy-induced hepatocellular carcinoma
Zhou, J., Zhang, X., Tang, H., Yu, J., Zu, X., Xie, Z., Yang, X., Hu, J., Tan, F., Li, Q., et al. (2020) · Clinica Chimica Acta · doi:10.1016/j.cca.2020.02.028 · Cited by 12
Nrf2-Keap1 Activation, A Promising Strategy in the Prevention of Cancer
Ojo, O. A., Ajiboye, B. O., Fadaka, A. O., Taro, P., & Shariati, M. A. (2016) · Free Radicals and Antioxidants · doi:10.5530/fra.2017.1.1 · Cited by 12
“• Shows ability to slow progression of and ‘kill’ cancer cell (Mitsuishi et al., 2012).”
Background
Amorphous Silica Nanoparticles Obtained by Laser Ablation Induce Inflammatory Response in Human Lung Fibroblasts
Voicu, S. N., Balaș, M., Stan, M. S., Trică, B., Șerban, A. I., Stanca, L., Hermenean, A. O., & Dinischiotu, A. (2019) · Materials · doi:10.3390/ma12071026 · Cited by 12
“One of these mediates the transcription of components of the pentose phosphate pathway that generates NADPH, which is an important reducing molecule in the framework of the antioxidant system [43].”
Background
Dietary supplementation with sulforaphane attenuates liver damage and heme overload in a sickle cell disease murine model
Panda, H., Keleku-Lukwete, N., Kuga, A., Fuke, N., Suganuma, H., Suzuki, M., & Yamamoto, M. P. (2019) · Experimental Hematology · doi:10.1016/j.exphem.2019.08.001 · Cited by 11
Self-citation
Reciprocal interference between the NRF2 and LPS signaling pathways on the immune‐metabolic phenotype of peritoneal macrophages
Mornata, F., Pepe, G., Sfogliarini, C., Brunialti, E., Rovati, G. E., Locati, M., Maggi, A. C., & Vegeto, E. (2020) · Pharmacology Research & Perspectives · doi:10.1002/prp2.638 · Cited by 12
The Expression of TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Can Be Controlled by the Antioxidant Orchestrator NRF2 in Human Carcinoma Cells
Simon‐Molas, H., Sánchez‐de‐Diego, C., Navarro‐Sabaté, À., Castaño, E., Ventura, F., Bartrons, R., & Manzano, À. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031905 · Cited by 13
“Constitutive activation of NRF2 is common in malignant cells regardless of ROS levels [16,17].”
Background
The Reduction in Urinary Glutamate Excretion Is Responsible for Lowering Urinary pH in Pink Urine Syndrome
Ogawa, S., Takiguchi, J., Shimizu, M., et al. (2016) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.239.103 · Cited by 12
Oxidative Stress and the Intersection of Oncogenic Signaling and Metabolism in Squamous Cell Carcinomas
Choe, J. H., Mazambani, S., Kim, T. H., & Kim, J. (2021) · Cells · doi:10.3390/cells10030606 · Cited by 14
“Furthermore, Nrf2 has been demonstrated to directly promote the PPP, nucleotide synthesis, NADPH production, and glutamine metabolism, especially in conjunction with active PI3K/AKT signaling, which promotes the nuclear accumulation of Nrf2 [157].”
BackgroundInfluential
Morin-VitaminE-β-CyclodextrinInclusionComplexLoadedChitosanNanoparticles (M-Vit.E-CD-CSNPs) Ameliorate Arsenic-Induced Hepatotoxicityina Murine Model
Mondal, S., Das, S., Mahapatra, P. K., et al. (2022) · Molecules · doi:10.3390/molecules27185819 · Cited by 11
NRF2 has a splicing regulatory function involving the survival of motor neuron (SMN) in non-small cell lung cancer
Cui, Q., Wang, W., Namani, A., Wang, H., Hammad, A., Huang, P., Gao, Y., Elshaer, M., Wu, Y., Wang, X. J., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02799-z · Cited by 11
“Similarly, through transcriptional transactivation, NRF2 directs anabolic metabolism by upregulating amino-acid metabolism, the pentose phosphate pathway, NADPH biosynthesis, nucleotide production, and fatty-acid oxidation, while suppressing NADPH‐consuming fatty-acid synthesis [9, 24, 25].”
Background

Authors: Mitsuishi, Y., Taguchi, K., Kawatani, Y., Shibata, T., Nukiwa, T., Aburatani, H., Yamamoto, M., & Motohashi, H.
Affiliations: Tohoku University (JP)
National Cancer Center Research Institute (JP)
Research Center for Advanced Science and Technology, The University of Tokyo (JP)
Corresponding author: Yamamoto, Masayuki
Motohashi, Hozumi
ORCID: Mitsuishi, Yoichiro
Taguchi, Keiko
Shibata, Tatsuhiro
Nukiwa, Toshihiro
Aburatani, Hiroyuki
Yamamoto, Masayuki
Motohashi, Hozumi
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2012-07
Volume: 22
Issue: 1
Pages: 66-79
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2012.05.016
OpenAlex: W2053047691
Semantic Scholar: 280f3f56ddaa915842258eabcbeb792646ef42a7
Cited by: 1,395
References: 49
Citations by year: 2026: 72 · 2025: 85 · 2024: 97 · 2023: 112 · 2022: 132 · 2021: 126 · 2020: 131 · 2019: 108 · 2018: 103 · 2017: 101 · 2016: 89 · 2015: 85 · 2014: 76 · 2013: 63 · 2012: 12
FWCI: 30.36
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 381 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science (23659166, 24249015, 24221011)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: Nrf2, tumor metabolic reprogramming, glucose metabolism, glutamine metabolism, anabolic metabolism, PI3K/Akt signaling, cell proliferation, redox homeostasis, cytoprotection
MeSH terms: Animals, Cell Division, Glucose, Glutamine, Mice, Transgenic, Neoplasms, Signal Transduction, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, NF-E2-Related Factor 2, Mice

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Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming

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