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Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
Open accessAbstract
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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“For example, NRF2 steers glucose to anabolic cancer metabolism and prevents oxidation of multiple translational factors to augment protein output [15,16].”
From NRF2 Activation Confers Resistance to eIF4A Inhibitors in Cancer Therapy (2021) · cites this paper as [16]
In the citing paper
“The aberrant activation of Nrf2 in cancer cells leads to increased expression of Glucose-6-phosphate dehydrogenase (G6PD), transketolase (TKT), 6-phosphogluconate dehydrogenase (PGD), and other metabolic enzymes promoting glutamine and glucose metabolism in pentose phosphate pathway (PPP) and increasing synthesis of amino acids participating in metabolic reprogramming required for cell prol”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Mitsuishi et al. 2012
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Cites
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244
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
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
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
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445
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
Regulation of glutathione synthesis
Lu, S. C.-L. (2008) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2008.05.005 · Cited by 2,131
Activation of a metabolic gene regulatory network downstream of mTOR complex 1
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
TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N. C., Nakano, K., Bartrons, R., Gottlieb, E., & Vousden, K. H. (2006) · Cell · doi:10.1016/j.cell.2006.05.036 · Cited by 2,019
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Favero, G. D., Zaharescu, R., & Marko, D. (2018) · Archives of Toxicology · doi:10.1007/s00204-018-2317-6 · Cited by 33
Multiple roles of Nrf2-Keap1 signaling
Deng, H. (2013) · Fly · doi:10.4161/fly.27007 · Cited by 33
“Nrf2 can prevent apoptosis through activating the anti-apoptotic factor Bcl-2,(46) control cell cycle through retinoblastoma protein,(47) and facilitate cancer cell growth through influencing glucose metabolism.(26) It is noticeable that Bcl-2, retinoblastoma, and glucose metabolism can all be regulated by Ras signali…”
The mechanistic insights of the antioxidant Keap1-Nrf2 pathway in oncogenesis: a deadly scenario
Mukherjee, A. G., & Gopalakrishnan, A. V. (2023) · Medical Oncology · doi:10.1007/s12032-023-02124-4 · Cited by 33
NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting
Panda, H., Rowland, N. G., Krall, C. M., Bowman, B. M., Major, M. B., & Zolkind, P. (2025) · Oncogene · doi:10.1038/s41388-025-03560-4 · Cited by 39
“A hallmark of NRF2-active tumors is metabolic reprogramming to promote glutamine metabolism, production of pentose phosphate pathway (PPP) intermediaries, and redox state effector proteins [77].”
Chartoumpekis, D. V., Ziros, P. G., Zaravinos, A., Iskrenova, R. P., Psyrogiannis, A. I., Kyriazopoulou, V. E., Sykiotis, G. P., & Habeos, I. G. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/340731 · Cited by 33
“It has been previously shown that Nrf2 can redirect glucose and glutamine to anabolic pathways in cancer cells, and Me-1 is implicated in these pathways [60]; however, these results in cancer cells cannot necessarily be safely extrapolated to nontransformed hepatocytes [61].”
BackgroundImportance of the Keap1-Nrf2 pathway in NSCLC: Is it a possible biomarker? (Review)
Rodríguez, R. B. (2018) · Biomedical Reports · doi:10.3892/br.2018.1143 · Cited by 32
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Li, Z., Wang, X., Su, Y., Gao, K., Chen, Y., Ma, L., & Xie, Y. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2019.110507 · Cited by 32
Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma
Clerici, S., & Boletta, A. (2020) · Cancers · doi:10.3390/cancers12113458 · Cited by 36
Okazaki, K., Anzawa, H., Katsuoka, F., Kinoshita, K., Sekine, H., & Motohashi, H. (2022) · The Journal of Biochemistry · doi:10.1093/jb/mvac013 · Cited by 33
Self-citationNakao, K., Minato, N., & Üemoto, S. (2015) · Springer eBooks · doi:10.1007/978-4-431-55651-0 · Cited by 34
Wang, Z., Xiong, L., Wang, G., Wan, W., Zhong, C., & Zu, H. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.11.009 · Cited by 32
“sponse contributed to proliferative and mitogenic signals downstream of Akt (Mitsuishi et al., 2012).”
InfluentialYasuda, D., Yuasa, A., Obata, R., Nakajima, M., Takahashi, K., Ohe, T., Ichimura, Y., Komatsu, M., Yamamoto, M. P., Imamura, R. M., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.10.008 · Cited by 33
Self-citationMallick, R., Bhowmik, P., & Duttaroy, A. K. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115591 · Cited by 35
Glutamine, Glucose and other Fuels for Cancer
Ruiz-Pérez, M. V., Sánchez‐Jiménez, F., Alonso, F. J., Segura, J., Márquez, J., & Medina, M. Á. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990482 · Cited by 31
Shimizu, T., Inoue, K.-I., Hachiya, H., Shibuya, N., Aoki, T., & Kubota, K. (2016) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.364 · Cited by 30
“Glucose-6-phosphate dehydrogenase (G6PD) and transketolase (TKT) are transcriptional targets of NRF2 [7].”
BackgroundCancer chemoprevention via activation of proteostatic modules
Sklirou, A. D., Papanagnou, E., Fokialakis, N., & Trougakos, I. P. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.10.034 · Cited by 32
Co-exposure to silver nanoparticles and cadmium induce metabolic adaptation in HepG2 cells
Miranda, R. R., Gorshkov, V., Korzeniowska, B., et al. (2018) · Nanotoxicology · doi:10.1080/17435390.2018.1489987 · Cited by 31
Role of Nrf2 in Pancreatic Cancer
Cykowiak, M., & Krajka‐Kuźniak, V. (2021) · Antioxidants · doi:10.3390/antiox11010098 · Cited by 31
Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer
Ackova, D. G., Maksimova, V., Smilkov, K., Buttari, B., Arese, M., & Saso, L. (2023) · Pharmaceuticals · doi:10.3390/ph16060850 · Cited by 34
“Some studies report that cancer cells can take control of the overactivated NRF2, with this factor even being a key player in the modulation of anabolic metabolism required for cancer cell growth and proliferation [70].”
BackgroundSequestosome 1/p62-related pathways as therapeutic targets in hepatocellular carcinoma
Denk, H., Stumptner, C., Abuja, P. M., & Zatloukal, K. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1601703 · Cited by 32
“Moreover, tumor cells also profit from metabolic reprogramming, since Nrf2 regulates the expression of genes involved in glutaminolysis, purine nucleotide and glutathione synthesis, and the pentose phosphate pathway [114,115].”
BackgroundAkıncı, E., Cha, M., Lin, L., Yeo, G. H. T., Hamilton, M. C., Donahue, C. J., Bermudez-Cabrera, H. C., Zanetti, L. C., Chen, M., Barkal, S. A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.27.270819 · Cited by 32
“Along with their role in increasing mitochondrial activity, both of these pathways promote purine biosynthesis 52,43 , a pathway whose activation should mitigate remdesivir toxicity.”
Chaperone-Mediated Autophagy in the Liver: Good or Bad?
Dash, S., Aydın, Y., & Moroz, K. (2019) · Cells · doi:10.3390/cells8111308 · Cited by 32
NRF2 Activation Confers Resistance to eIF4A Inhibitors in Cancer Therapy
Sanghvi, V. R., Mohan, P., Singh, K., Cao, L., Berishaj, M., Wolfe, A. L., Schatz, J. H., Lailler, N., de Stanchina, E., Viale, A., et al. (2021) · Cancers · doi:10.3390/cancers13040639 · Cited by 27
“For example, NRF2 steers glucose to anabolic cancer metabolism and prevents oxidation of multiple translational factors to augment protein output [15,16].”
BackgroundYuan, Y., Guan, H., Huang, Y., Luo, J., Jian, J., Cai, S., & Yang, S. (2023) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2023.108547 · Cited by 30
Lee, H. M., Muhammad, N., Lieu, E. L., Cai, F., Mu, J., Ha, Y., Cao, G., Suchors, C., Joves, K., Chronis, C., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01066-z · Cited by 33
“This might also explain the high frequency of somatic mutations in KEAP1 and NRF2 in NSCLC. Tumours with KEAP1 loss and NRF2 activation mitigate oxidative stress by inducing various enzymes that produce cytosolic NADPH 63,64 .”
Sheng, W., Yue, Y., Qi, T., Qin, H., Liu, P., Wang, D., Zeng, H., & Yu, F. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s479186 · Cited by 31
“112,113 Furthermore, although NRF2 activators may show positive effects in the short term, the safety and side effects of long-term use still require further investigation.”
BackgroundExpression of nuclear factor, erythroid 2-like 2-mediated genes differentiates tuberculosis
Qian, Z., Lv, J., Kelly, G. T., Wang, H., Zhang, X., Gu, W., Yin, X., Wang, T., & Zhou, T. (2016) · Tuberculosis · doi:10.1016/j.tube.2016.04.008 · Cited by 27
“To elucidate the genes potentially regulated by Nrf2, we compared the global gene expression profiles between A549 control cells and Nrf2-deficient cells [15], which were obtained from the Gene Expression Omnibus (GEO) [26] database (GEO accession: GSE38332).”
MethodMoriyama, T., Tanaka, S., Nakayama, Y., Fukumoto, M., Tsujimura, K., Yamada, K., Bamba, T., Yoneda, Y., Fukusaki, E., & Oka, M. (2016) · Scientific Reports · doi:10.1038/srep34648 · Cited by 30
Cullin 3 and Its Role in Tumorigenesis
Chen, R. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-1025-0_12 · Cited by 29
L-lactate exerts a pro-proliferative effect on adult hippocampal precursor cells in vitro
Pötzsch, A., Zocher, S., Bernas, S. N., Leiter, O., Rünker, A. E., & Kempermann, G. (2021) · iScience · doi:10.1016/j.isci.2021.102126 · Cited by 36
Uncovering the Metabolic and Stress Responses of Human Embryonic Stem Cells to FTH1 Gene Silencing
Scaramuzzino, L., Lucchino, V., Scalise, S., Conte, M. L., Zannino, C., Sacco, A., Biamonte, F., Parrotta, E. I., Costanzo, F. S., & Cuda, G. (2021) · Cells · doi:10.3390/cells10092431 · Cited by 30
“This finding perfectly matches with the fact that high glucose levels are required for the proper functionality of detox systems, such as the pentose phosphate (PPP), glucuronidation, and glutathione biosynthesis pathways, all of which are finely tuned by Nrf2 [56,57].”
BackgroundDual role of Nrf2 in cancer: molecular mechanisms, cellular functions and therapeutic interventions
Poornashree, M., Kumar, H., AJMEER, R., Jain, R., & Jain, V. K. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-08126-1 · Cited by 28
“The PI3K pathway, the Nrf2 Kirsten rat sarcoma virus oncogene and B-Raf are all examples of oncogenes [30, 31].”
BackgroundNrf2 activation improves experimental rheumatoid arthritis
Zhang, A., Suzuki, T., Adachi, S., Yoshida, E., Sakaguchi, S., & Yamamoto, M. P. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.07.016 · Cited by 30
Self-citationTerraneo, L., Virgili, E., Caretti, A., Bianciardi, P., & Samaja, M. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.03.019 · Cited by 31
NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis
Lister, A., Bourgeois, S., Silva, P. H. I., Rubio‐Aliaga, I., Marbet, P., Walsh, J., Shelton, L. M., Keller, B., Verrey, F., Devuyst, O., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-24000-2 · Cited by 29
Kujundžić, R. N., Stepanić, V., Milković, L., Gašparović, A. Č., Tomljanović, M., & Gall‐Tros̆elj, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051180 · Cited by 31
Žarković, N., Gęgotek, A., Łuczaj, W., Jaganjac, M., Šunjić, S. B., Žarković, K., & Skrzydlewska, E. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2904153 · Cited by 31
Gene regulatory effects of disease-associated variation in the NRF2 network
Lacher, S. E., & Slattery, M. G. (2016) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2016.09.001 · Cited by 27
Nguyen, V. T., Fuse, Y., Tamaoki, J., Akiyama, S.-I., Muratani, M., Tamaru, Y., & Kobayashi, M. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/5720574 · Cited by 28
“Nrf2 regulates the protein turnover by inducing proteasome subunits to confer protective effects against chronic diseases [4] and modifies cellular metabolic processes, for example, the pentose phosphate pathway, which provides NADPH and purine nucleotides that are essential for the redox homeostasis and cellular prol…”
BackgroundNault, R., Doskey, C. M., Fader, K. A., Rockwell, C. E., & Zacharewski, T. R. (2018) · Molecular Pharmacology · doi:10.1124/mol.118.112144 · Cited by 28
“…(AREs), and tended to be associated with detoxification mechanisms involving the induction of xenobiotic metabolism and/or Warburg-like metabolic reprogramming to support cell survival from toxic insult (Wu et al., 2011; Mitsuishi et al., 2012a,b; Nault et al., 2016b; Bortoli et al., 2018).”
BackgroundInfluentialZhang, X., Liang, Y., Xu, H., Zhou, Q., Tan, B., Yi, Q., Liang, Y., Xie, M., Zhang, Y., Tian, J., et al. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02264-2 · Cited by 29
Knatko, E. V., Higgins, M., Fahey, J. W., & Dinkova‐Kostova, A. T. (2016) · Scientific Reports · doi:10.1038/srep25804 · Cited by 28
Zhang, B., Wu, J., Cai, Y., Luo, M., Wang, B., & Gu, Y. (2019) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmz015 · Cited by 35
Beyond Antioxidation: Keap1–Nrf2 in the Development and Effector Functions of Adaptive Immune Cells
Pant, A., Dasgupta, D., Tripathi, A., & Pyaram, K. (2023) · ImmunoHorizons · doi:10.4049/immunohorizons.2200061 · Cited by 28
“Given that Nrf2 is a well-known regulator of glucose and glutamine metabolism (14, 80), and T cell subsets rely heavily on these nutrients for their effector functions, further studies are necessary to examine whether and how Nrf2 modulates nutrient metabolism in these immune cell subsets.”
BackgroundPaeonol ameliorates hyperlipidemia and autophagy in mice by regulating Nrf2 and AMPK/mTOR pathways
Shen, B., Wen, Y., Li, S., Zhou, Y., Chen, J., Yang, J., Zhao, C., & Wang, J. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155839 · Cited by 28
Bocca, C., Nzoughet, J. K., Leruez, S., Amati‐Bonneau, P., Ferré, M., Kane, M.-S., Veyrat‐Durebex, C., de la Barca, J. M. C., Chevrollier, A., Homedan, C., et al. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-23027 · Cited by 27
“NRF2 is a transcription factor whose activity, among others, influences the cellular redox status and regulates de novo purine biosynthesis.(34,35) The alteration of purine concentrations could be particularly relevant to explain the pathophysiology of OPA1-related disorders.”
BackgroundUVA , metabolism and melanoma: UVA makes melanoma hungry for metastasis
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Klóska, D., Kopacz, A., Cysewski, D., Aepfelbacher, M., Dulak, J., Józkowicz, A., & Grochot‐Przeczek, A. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7505 · Cited by 30
“This possibility is, however, rather unlikely, because chromatin immunoprecipitation-sequencing (ChIP-seq) analyses done in human nonsmall-cell lung cancer cell line A549 and six human lymphoblastoid cell lines did not identify any other Nrf2 binding sequence apart from ARE (4, 41).”
Higuchi, H., Kamimura, D., Jiang, J., Atsumi, T., Iwami, D., Hotta, K., Harada, H., Takada, Y., Kanno‐Okada, H., Hatanaka, K. C., et al. (2020) · International Immunology · doi:10.1093/intimm/dxaa003 · Cited by 27
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“Besides, the activation of PI3K-Akt pathway promotes the nuclear accumulation of NRF2 to reinforce the metabolic reprogramming of cancer cells [14].”
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Bosso, M., Haddad, D., Madhoun, A. S. A., & Al‐Mulla, F. (2024) · Biomedicines · doi:10.3390/biomedicines12010211 · Cited by 26
“However, studies over the last decade reveal a “dark side” of NRF2 [272], where its constitutive stabilization leads to increased glutaminolysis [273], cancer progression [274], metastasis [275], and chemoresistance [276,277].”
BackgroundRen, J., Ren, B., Liu, X., Cui, M., Fang, Y., Wang, X., Zhou, F., Gu, M., Xiao, R., Bai, J., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216649 · Cited by 30
Downregulation of Keap1 Confers Features of a Fasted Metabolic State
Knatko, E. V., Tatham, M. H., Zhang, Y., Castro, C., Higgins, M., Naidu, S. D., Leonardi, C., de la Vega, L., Honda, T., Griffin, J. L., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101638 · Cited by 26
Gan, L., Wang, W., Jiang, J., Tian, K., Liu, W., & Cao, Z. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1429836 · Cited by 29
Metabolic Signaling in the Tumor Microenvironment
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Gao, F., Li, J., Xi, C., Li, H., Liu, Y., Wang, Y.-P., & Xuan, L. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-018-0189-1 · Cited by 26
MTHFD1L-Mediated Redox Homeostasis Promotes Tumor Progression in Tongue Squamous Cell Carcinoma
Li, H., Fu, X., Fan, Y., Tian, T., Wang, C., & Yang, A. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01278 · Cited by 26
“Previous studies have demonstrated that MTHFD1L is transcriptionally regulated by the transcription factor nuclear factor (erythroid-derived 2)like 2 (NRF2) (18), which acts as the central regulator for redox homeostasis (38).”
BackgroundZborowski, V. A., Heck, S. O., Vencato, M., Pinton, S., Marques, L. S., & Nogueira, C. W. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05372-3 · Cited by 26
Panda, H., Suzuki, M., Naito, M., Saito, R., Wen, H., Baird, L., Uruno, A., Miyata, K., & Yamamoto, M. P. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.05.017 · Cited by 27
Self-citationNovel NRF2 ‐activated cancer treatments utilizing synthetic lethality
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Self-citationNRF2 , a crucial modulator of skin cells protection against vitiligo, psoriasis, and cancer
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“Importantly, PPP was shown to maintain glutathione in its reduced state and is critical for NRF2-induced proliferation.(43) NRF2 also regulates enzymes related to the nucleotide biosynthesis pathway (phosphoribosyl pyrophosphate amidotransferase; methylenetetrahydrofolate dehydrogenase 2), glucuronidation pathway (UDP…”
BackgroundArolt, C., Dugan, M. H., Wild, R., Richartz, V., Holz, B., Scheel, A. H., Brägelmann, J., Wagener‐Ryczek, S., Merkelbach‐Bruse, S., Wolf, J., et al. (2023) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2023.07.016 · Cited by 26
Genetic polymorphism in the NRF2 gene as a prognosis marker for cancer chemotherapy
Ishikawa, T. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00383 · Cited by 27
“…hand, have shown that NRF2 contributes to cancer cell proliferation, drug resistance, and metabolic re-programming, as well (Kwak et al., 2002; Lau et al., 2008; Hayes and McMahon, 2009; Homma et al., 2009; Taguchi et al., 2011; Mitsuishi et al., 2012; Sporn and Liby, 2012; Yamadori et al., 2012).”
BackgroundMitochondrial Dysfunction and Disturbed Coherence: Gate to Cancer
Pokorný, J., Pokorný, J., Foletti, A., Kobilková, J., Vrba, J., & Vrba, J. (2015) · Pharmaceuticals · doi:10.3390/ph8040675 · Cited by 26
“However, in transformed cells glutamine is often redirected into anabolic pathways [84].”
BackgroundThe Role of Reactive Oxygen Species in Epilepsy
Kovac, S., Dinkova‐Kostova, A. T., & Abramov, A. Y. (2016) · Reactive Oxygen Species · doi:10.20455/ros.2016.807 · Cited by 26
“, malic enzyme 1 (ME1), isocitrate dehydrogenase 1 (IDH1), glucose-6-phosphate dehydrogenase (G6PD), and 6-phosphogluconate dehydrogenase (PGD) [100–103].”
BackgroundSenger, D. R., Hoang, M. V., Kim, K. H., Li, C., & Cao, S. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.09.017 · Cited by 26
Homeostatic Role of Autophagy in Hepatocytes
Khambu, B., Yan, S., Huda, N., Liu, G., & Yin, X. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1669939 · Cited by 28
Cuadrado, A., Cazalla, E., Bach, A., Bathish, B., Naidu, S. D., DeNicola, G. M., Dinkova-Kostova, A. T., Fernández-Ginés, R., Grochot-Przeczek, A., Hayes, J. D., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103569 · Cited by 28
“NRF2 also promotes glutamine uptake and its incorporation into GSH to promote radiation resistance [280,281], thereby conferring dependence on glutamine and the glutamine transporter ASCT2 [267].”
InfluentialSelf-citationHasan, S. K., Jayakumar, S., Barroso, E. E., Jha, A., Catalano, G., Sandur, S. K., & Noguera, N. I. (2025) · Cells · doi:10.3390/cells14100713 · Cited by 31
“…nucleus and inducing preferential transcription Cano et al. G6PD, transaldolase 1 (TALDO1), and transketolase ( Nrf2-dependent cells where active [54]. recovery, Nrf2 activation is required to induce the PPP, and inhibition of the PPP disrupts nucleotide biosynthesis, thereby preventing liver…”
InfluentialNRF2: Master regulator of cellular homeostasis and therapeutic vulnerability in cancer
Chen, W.-T., McKee, N. W., Kuhnell, D., & Dodson, M. B. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104050 · Cited by 29
“…and GSH to reduce reactive species, most of the enzymes responsible for regenerating NAPDH, namely glucose-6-phosphate dehydrogenase ( G6PD) of the pentose phosphate pathway, and malic enzyme 1 ( ME1 ) and isocitrate dehydrogenase 1 ( IDH1 ) of the citric acid cycle are also target genes [107].”
Sakai, E., Morita, M., Ohuchi, M., Kido, M. A., Fukuma, Y., Nishishita, K., Okamoto, K., Itoh, K., Yamamoto, M. P., & Tsukuba, T. (2017) · The FASEB Journal · doi:10.1096/fj.201700177r · Cited by 26
“Primers used in this study were previously described (15, 19, 20) or as follows: Bglap 59-CGCTCTGTCTCTCTGACCTC-39 (forward) and 39-GACTGAGGCTCCAAGGTAGC-59 (reverse); Ctsk: 59-CAGCTTCCCCAAGATGTGAT-39 (forward) and 39-AGCACCAACGAGAGGAGAAA-59 (reverse); Dc-stamp: 59-CTAGCTGGCTGGACTTCATCC-39 (forward) and 39-TCATGCTGTCTAG…”
BackgroundSelf-citationKerins, M. J., Liu, P., Tian, W., Mannheim, W., Zhang, D. D., & Ooi, A. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00037-19 · Cited by 25
ERBB3 and IGF1R Signaling Are Required for Nrf2-Dependent Growth in KEAP1-Mutant Lung Cancer
Vartanian, S., Lee, J., Klijn, C. N., Gnad, F., Bagniewska, M., Schaefer, G., Zhang, D., Tan, J., Watson, S. A., Liu, L., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2086 · Cited by 25
“Cancer Res; 79(19) October 1, 2019 Cancer Research 4834”
BackgroundInfluentialLu, X., Lin, Y., Qiu, X., Liu, J., Zhu, T., Araujo, J. A., Zhang, J. J., & Zhu, Y. (2021) · Environmental Science & Technology · doi:10.1021/acs.est.0c07627 · Cited by 25
Identification of a Stable, Non-Canonically Regulated Nrf2 Form in Lung Cancer Cells
Mikac, S., Rychłowski, M., Dziadosz, A., Szabelska‐Beręsewicz, A., Fåhræus, R., Hupp, T. R., & Sznarkowska, A. (2021) · Antioxidants · doi:10.3390/antiox10050786 · Cited by 26
“Nrf2 also has an effect on metabolic reprogramming, redirecting glucose and glutamine to synthesis pathways of purine nucleotides, glutathione, and serine [8].”
BackgroundThe nexus between redox state and intermediary metabolism
Zoccarato, A., Nabeebaccus, A., Oexner, R. R., Santos, C. X. C., & Shah, A. M. (2021) · FEBS Journal · doi:10.1111/febs.16191 · Cited by 27
The emerging potential role of p62 in cancer treatment by regulating metabolism
Zhang, X., Dai, M., Li, S., Li, M., Cheng, B., Ma, T., & Zhou, Z. G. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.05.004 · Cited by 30
Ohnuma, T., Anzai, E., Suzuki, Y., Shimoda, M., Saito, S., Nishiyama, T., Ogura, K., & Hiratsuka, A. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2015.09.007 · Cited by 26
Cai, M., Chen, M., Ma, P., Wu, J., Lu, H., Zhang, S., Liu, J., Zhao, X., Zhuang, G., Yu, Z., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.31975 · Cited by 25
Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities
Turdo, A., Porcelli, G., D’Accardo, C., Franco, S. D., Verona, F., Forte, S., Giuffrida, D., Memeo, L., Todaro, M., & Stassi, G. (2020) · Cancers · doi:10.3390/cancers12061436 · Cited by 27
Pehar, M., Ball, L. E., Sharma, D. R., Harlan, B. A., Comte‐Walters, S., Neely, B. A., & Vargas, M. R. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.049288 · Cited by 26
“branch, all direct targets of Nrf2 (39, 40).”
BackgroundInfluentialMitochondrial signaling pathways and their role in cancer drug resistance
Sharma, A., Virmani, T., Kumar, G., Sharma, A., Virmani, R., Gugulothu, D. B., Singh, K., Misra, S. K., Pathak, K., Chitranshi, N., et al. (2024) · Cellular Signalling · doi:10.1016/j.cellsig.2024.111329 · Cited by 28
Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management
Dewanjee, S., Bhattacharya, H., Bhattacharyya, C., Chakraborty, P., Fleishman, J. S., Alexiou, A. T., Papadakis, M., & Jha, S. K. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01878-2 · Cited by 29
“Nrf2 redirects glucose and glutamine into anabolic pathways under the influence of PI3K-Akt signaling [57].”
BackgroundNrf2 plays a critical role in the metabolic response during and after spaceflight
Uruno, A., Saigusa, D., Suzuki, T., Yumoto, A., Nakamura, T., Matsukawa, N., Yamazaki, T., Saito, R., Taguchi, K., Suzuki, M., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02904-6 · Cited by 25
Self-citationHIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer
Hamada, S., Matsumoto, R., & Masamune, A. (2022) · Cancers · doi:10.3390/cancers14020411 · Cited by 24
“Lung cancer cells with constitutive NRF2 activation altered amino acid metabolism and purine nucleotide synthesis, yielding growth advantages [103].”
BackgroundBRD4 Targets the KEAP1-Nrf2-G6PD Axis and Suppresses Redox Metabolism in Small Cell Lung Cancer
Lv, Y., Lv, X., Zhang, J., Cao, G., Xu, C., Zhang, B., & Lin, W. (2022) · Antioxidants · doi:10.3390/antiox11040661 · Cited by 25
“In the past decades, accumulating data have indicated that the flux of the PPP is increased in response to the tumor microenvironment and intracellular demands to promote cancer cell proliferation and survival across cancers [6,7].”
BackgroundTumour Stem Cells in Breast Cancer
Ibragimova, M. K., Tsyganov, M. M., & Литвяков, Н. В. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095058 · Cited by 27
“NRF2 can push dormant tumour cells to proliferate or bypass metabolic blocks [31].”
BackgroundLastra, D., Escoll, M., & Cuadrado, A. (2022) · Antioxidants · doi:10.3390/antiox11050946 · Cited by 24
“Not surprisingly, many studies have reported pro–tumoral effects associated with these cytoprotective functions, including ROS scavenging [5], chemoresistance and radioresistance [6–8], metabolic reprogramming towards anabolic pathways and the pentose phosphate pathway [9], or evasion of apoptosis [10,11].”
BackgroundBernuzzi, F., Märtens, A., Saha, S., Troncoso‐Rey, P., Ludwig, T., Hiller, K., Mithen, R. F., Korcsmáros, T., & Τράκα, Μ. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102878 · Cited by 25
SLAM-ITseq identifies that Nrf2 induces liver regeneration through the pentose phosphate pathway
Tan, V. W. T., Salmi, T. M., Karamalakis, A. P., Gillespie, A., Ong, A. J. S., Balic, J. J., Chan, Y.-C., Bladen, C. E., Brown, K., Dawson, M. A., et al. (2024) · Developmental Cell · doi:10.1016/j.devcel.2024.01.024 · Cited by 24
Intersections between mitochondrial sirtuin signaling and tumor cell metabolism
Herrera, K. N. G., Lee, J. J., & Haigis, M. C. (2015) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2015.1031879 · Cited by 25
“Additionally, tumor suppressors, such as p53 and Nrf2, not discussed in this review, also rewire the metabolic landscape of a cancer cell (Liang et al., 2013; Mitsuishi et al., 2012).”
McMahon, M. J., Campbell, K. H., MacLeod, A. K., McLaughlin, L. A., Henderson, C. J., & Wolf, C. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114055 · Cited by 24
Autocrine and Paracrine Regulation of Keratinocyte Proliferation through a Novel Nrf2–IL-36γ Pathway
Kurinna, S. M., Muzumdar, S., Köhler, U. A., Kockmann, T., Keller, U. A. D., Schäfer, M., & Werner, S. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1501447 · Cited by 24
“This causes enhanced drug resistance, increased survival under stress conditions, and hyperproliferation of the tumor cells as a result of an increased abundance of multidrug-resistance proteins, ROSdetoxifying enzymes, and metabolic enzymes (2, 3).”
BackgroundUrinary pH is a predictor of diabetes in men; a population based large scale cohort study
Hashimoto, Y., Hamaguchi, M., Nakanishi, N., et al. (2017) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2017.04.023 · Cited by 24
Yamaguchi, Y., Kamai, T., Higashi, S., Murakami, S., Arai, K., Shirataki, H., & Yoshida, K. (2019) · BMC Cancer · doi:10.1186/s12885-019-6347-0 · Cited by 25
Lipid Peroxidation-Related Redox Signaling in Osteosarcoma
Šunjić, S. B., Jaganjac, M., Vlainić, J., Halasz, M., & Žarković, N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084559 · Cited by 24
“…receptor (AHR) [194]; nuclear factor (NF)- κ B; extracellular signal-regulated protein kinases (ERK) [195]; c-jun JNK [195], PI3K-AKT, and p38 MAPK [196,197]; protein kinase C (PKC) [198], casein kinase 2 (CK2) [199]; and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) [200].”
BackgroundInfluentialRealigned transsulfuration drives BRAF-V600E-targeted therapy resistance in melanoma
Borbényi-Galambos, K., Erdélyi, K., Ditrói, T., Jurányi, E. P., Szántó, N., Szatmári, R. Z., Czikora, Á., Schmidt, E. E., Garai, D., Cserepes, M., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.01.021 · Cited by 26
Bazmandegan, G., Zamanian, M. Y., Giménez‐Llort, L., Nikbakhtzadeh, M., Kamiab, Z., & Heidari, M. (2022) · Current Molecular Pharmacology · doi:10.2174/1874467215666220620143655 · Cited by 24
Metadata
- 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
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 22
- Issue
- 1
- Pages
- 66-79
- ISSN
- 1535-6108 (ISSN-L)
- 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
- 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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