Glioma-Derived Mutations in IDH1 Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1α
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Heterozygous mutations in the gene encoding isocitrate dehydrogenase-1 ( IDH1 ) occur in certain human brain tumors, but their mechanistic role in tumor development is unknown. We have shown that tumor-derived IDH1 mutations impair the enzyme's affinity for its substrate and dominantly inhibit wild-type IDH1 activity through the formation of catalytically inactive heterodimers. Forced expression of mutant IDH1 in cultured cells reduces formation of the enzyme product, α-ketoglutarate (α-KG), and increases the levels of hypoxia-inducible factor subunit HIF-1α, a transcription factor that facilitates tumor growth when oxygen is low and whose stability is regulated by α-KG. The rise in HIF-1α levels was reversible by an α-KG derivative. HIF-1α levels were higher in human gliomas harboring an IDH1 mutation than in tumors without a mutation. Thus, IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis in part through induction of the HIF-1 pathway.
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HIF is stabilized in IDH-associated gliomas, and this has been proposed to result from intracellular 2OG depletion following IDH loss of function.
“HIF is stabilized in IDH-associated gliomas; this has been proposed to be a consequence of intracellular depletion of 2OG following IDH loss of function (Zhao et al, 2009).”
From The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases (2011) · cites this paper as Zhao et al, 2009
IDH mutations occur at substrate-binding arginine residues and inactivate IDH for conversion of isocitrate to 2OG.
“The IDH mutations occur at substrate-binding arginine residues (Arg 132 in IDH1; Arg 140 and Arg 172 in IDH2) and inactivate IDH for conversion of isocitrate to 2-oxoglutarate (2OG; Zhao et al, 2009).”
From The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases (2011) · cites this paper as Zhao et al, 2009
Overexpression of IDH1 Arg132 mutants results in elevated HIFα levels.
“Overexpression of IDH1 Arg 132 mutants results in elevated HIFa levels (Zhao et al, 2009).”
From The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases (2011) · cites this paper as Zhao et al, 2009
The stability of HIF-1α is regulated by α-KG, and increasing α-KG reduces HIF-1α expression.
“The stability of HIF‐1α is regulated by α‐KG, and increasing α‐KG reduces the expression of HIF‐1α.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [168]
Inhibiting SDH during ischaemia by preloading tissues with DMM prevents succinate accumulation during ischaemia and protects against tissue damage upon reperfusion.
“Inhibiting the mitochondrial enzyme SDH during ischaemia by preloading tissues with the SDH inhibitor DMM prevented succinate accumulation during ischaemia and protected against tissue damage upon reperfusion150.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [150]
Succinate accumulates during ischaemia and is oxidised upon reperfusion to drive mitochondrial superoxide formation that contributes to ischaemia-reperfusion injury.
“succinate accumulated during ischaemia and is then oxidised upon reperfusion to drive the mitochondrial superoxide formation that contributes to ischaemia-reperfusion (IR) injury150,151.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [150]
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Cites
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857 · see citing works
<i>IDH1</i> and <i>IDH2</i> Mutations in Gliomas
Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808710 · Cited by 5,847 · see citing works
Malignant astrocytic glioma: genetics, biology, and paths to treatment
Furnari, F. B., Fenton, T., Bachoo, R. M., Mukasa, A., Stommel, J. M., Stegh, A., Hahn, W. C., Ligon, K. L., Louis, D. N., Brennan, C., et al. (2007) · Genes & Development · doi:10.1101/gad.1596707 · Cited by 2,316 · see citing works
Analysis of the IDH1 codon 132 mutation in brain tumors
Balss, J., Meyer, J., Mueller, W., Korshunov, A., Hartmann, C., & von Deimling, A. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0455-2 · Cited by 1,036 · see citing works
Xu, X., Zhao, J., Xu, Z., Peng, B., Huang, Q., Arnold, E., & Ding, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404298200 · Cited by 407 · see citing works
Self-citationBleeker, F. E., Lamba, S., Leenstra, S., Troost, D., Hulsebos, T. J. M., Vandertop, W. P., Frattini, M., Molinari, F., Knowles, M. A., Cerrato, A., et al. (2009) · Human Mutation · doi:10.1002/humu.20937 · Cited by 365 · see citing works
Evaluation of HIF-1 inhibitors as anticancer agents
Semenza, G. L. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.08.006 · Cited by 363 · see citing works
MacKenzie, E. D., Selak, M. A., Tennant, D. A., Payne, L. J., Crosby, S., Frederiksen, C. M., Watson, D. G., & Gottlieb, E. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01927-06 · Cited by 359 · see citing works
Cellular concentrations of enzymes and their substrates
Albe, K. R., Butler, M. H., & Wright, B. E. (1990) · Journal of Theoretical Biology · doi:10.1016/s0022-5193(05)80266-8 · Cited by 318 · see citing works
Multiple NADPH-producing pathways control glutathione (GSH) content in retina
Winkler, B. S., Desantis, N. M., & Solomon, F. (1986) · Experimental Eye Research · doi:10.1016/s0014-4835(86)80013-6 · Cited by 106 · see citing works
Soundar, S., Danek, B. L., & Colman, R. F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5606 · Cited by 38 · see citing works
Ingebretsen, O. C. (1976) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(76)90180-7 · Cited by 32 · see citing works
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Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · see citing works
Regulation of cancer cell metabolism
Cairns, R. A., Harris, I. S., & Mak, T. W. (2011) · Nature Reviews Cancer · doi:10.1038/nrc2981 · Cited by 4,744 · see citing works
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154 · see citing works
Otto Warburg's contributions to current concepts of cancer metabolism
Koppenol, W. H., Bounds, P. L., & Dang, C. V. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3038 · Cited by 3,427 · see citing works
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
Ward, P. S., & Thompson, C. B. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.014 · Cited by 3,233 · see citing works
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057 · see citing works
Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875 · see citing works
Self-citationHypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380 · see citing works
Recurring mutations found by sequencing an acute myeloid leukemia genome
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903840 · Cited by 2,219 · see citing works
Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., Cross, J. R., Fantin, V. R., Hedvat, C. V., Perl, A. E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.020 · Cited by 2,020 · see citing works
“Therefore, it has been proposed that mutant IDH1 can act as a dominant negative against wild-type IDH1 function, resulting in a decrease in cytosolic a-ketoglutarate levels and leading to an indirect activation of the HIF-1a pathway (Zhao et al., 2009).”
BackgroundDefining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics
Semenza, G. L. (2010) · Oncogene · doi:10.1038/onc.2009.441 · Cited by 1,712 · see citing works
HIF-1: upstream and downstream of cancer metabolism
Semenza, G. L. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.10.009 · Cited by 1,381 · see citing works
Exciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma
Van Meir, E. G., Hadjipanayis, C. G., Norden, A. D., Shu, H. K., Wen, P. Y., & Olson, J. J. (2010) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20069 · Cited by 1,372 · see citing works
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations
Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335 · see citing works
DNA damage and the balance between survival and death in cancer biology
Roos, W. P., Thomas, A. D., & Kaina, B. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.2 · Cited by 1,189 · see citing works
Xiao, M., Yang, H., Xu, W., Ma, S., Lin, H., Zhu, H., Liu, L., Liu, Y., Yang, C., Xu, Y., et al. (2012) · Genes & Development · doi:10.1101/gad.191056.112 · Cited by 1,188 · see citing works
“…and gain of activities in the production of a-ketoglutarate (a-KG) and 2-hydroxyglutarate (2-HG), respectively (Dang et al. 2009; Yan et al. 2009; Zhao et al. 2009). a-KG plays critical roles in four different metabolic and cellular pathways: as an intermediate in the Krebs cycle for energy…”
BackgroundSelf-citationHartmann, C. J., Meyer, J., Balß, J., Capper, D., Mueller, W. C., Christians, A., Felsberg, J., Wolter, M., Mawrin, C., Wick, W., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0561-9 · Cited by 1,163 · see citing works
Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology
Semenza, G. L. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104720 · Cited by 1,159 · see citing works
The Definition of Primary and Secondary Glioblastoma
Ohgaki, H., & Kleihues, P. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3002 · Cited by 1,125 · see citing works
The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases
Chowdhury, R., Yeoh, K. K., Tian, Y., Hillringhaus, L., Bagg, E. A., Rose, N. R., Leung, I. K. H., Li, X. S., Woon, E. C. Y., Yang, M., et al. (2011) · The EMBO Reports · doi:10.1038/embor.2011.43 · Cited by 1,035 · see citing works
Amary, M. F., Bacsi, K., Maggiani, F., Damato, S., Halai, D., Berisha, F., Pollock, R., O'Donnell, P., Grigoriadis, A., Diss, T., et al. (2011) · The Journal of Pathology · doi:10.1002/path.2913 · Cited by 1,023 · see citing works
Metabolic requirements for the maintenance of self-renewing stem cells
Ito, K., & Suda, T. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3772 · Cited by 1,014 · see citing works
How cancer metabolism is tuned for proliferation and vulnerable to disruption
Schulze, A., & Harris, A. L. (2012) · Nature · doi:10.1038/nature11706 · Cited by 927 · see citing works
RNA N6-methyladenosine modification in cancers: current status and perspectives
Deng, X., Su, R. J., Weng, H., Huang, H., Li, Z., & Chen, J. (2018) · Cell Research · doi:10.1038/s41422-018-0034-6 · Cited by 848 · see citing works
Self-citationMetabolomics and Isotope Tracing
Jang, C., Chen, L., & Rabinowitz, J. D. (2018) · Cell · doi:10.1016/j.cell.2018.03.055 · Cited by 841 · see citing works
Carr, E. L., Kelman, A., Wu, G. S., Gopaul, R., Senkevitch, E., Aghvanyan, A., Turay, A. M., & Frauwirth, K. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903586 · Cited by 830 · see citing works
Hartmann, C. J., Hentschel, B., Wick, W., Capper, D., Felsberg, J., Simon, M., Westphal, M., Schackert, G., Meyermann, R., Pietsch, T., et al. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0781-z · Cited by 823 · see citing works
Wick, W., Hartmann, C. J., Engel, C., Stoffels, M., Felsberg, J., Stockhammer, F., Sabel, M., Koeppen, S., Ketter, R., Meyermann, R., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.6497 · Cited by 803 · see citing works
Paschka, P., Schlenk, R. F., Gaidzik, V. I., Habdank, M., Krönke, J., Bullinger, L., Späth, D., Käyser, S., Zucknick, M., Götze, K. S. S., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.3762 · Cited by 803 · see citing works
Wolf, A., Agnihotri, S., Micallef, J., Mukherjee, J., Sabha, N., Cairns, R., Hawkins, C., & Guha, A. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20101470 · Cited by 789 · see citing works
Metabolic reprogramming and epigenetic modifications on the path to cancer
Sun, L., Zhang, H., & Gao, P. (2021) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 796 · see citing works
SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization
Finley, L. W. S., Carracedo, A., Lee, J., Souza, A., Egia, A., Zhang, J., Teruya-Feldstein, J., Moreira, P. I., Cardoso, S. M., Clish, C. B., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.02.014 · Cited by 782 · see citing works
Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma
Huse, J. T., & Holland, E. C. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2818 · Cited by 765 · see citing works
Gross, S., Cairns, R. A., Minden, M. D., Driggers, E. M., Bittinger, M. A., Jang, H. G., Sasaki, M., Jin, S., Schenkein, D. P., Su, S. M., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20092506 · Cited by 736 · see citing works
Borger, D. R., Tanabe, K. K., Fan, K. C., Lopez, H. U., Fantin, V. R., Straley, K. S., Schenkein, D. P., Hezel, A. F., Ancukiewicz, M., Liebman, H. M., et al. (2012) · The Oncologist · doi:10.1634/theoncologist.2011-0386 · Cited by 728 · see citing works
Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation
Koivunen, P., Lee, S., Duncan, C. G., Lopez, G., Lu, G., Ramkissoon, S., Losman, J. A., Joensuu, P., Bergmann, U., Gross, S., et al. (2012) · Nature · doi:10.1038/nature10898 · Cited by 727 · see citing works
Metabolic targets for cancer therapy
Galluzzi, L., Kepp, O., Heiden, M. G. V., & Kroemer, G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4145 · Cited by 705 · see citing works
IDH1 Mutations as Molecular Signature and Predictive Factor of Secondary Glioblastomas
Nobusawa, S., Watanabe, T., Kleihues, P., & Ohgaki, H. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0715 · Cited by 707 · see citing works
IDH mutation in glioma: molecular mechanisms and potential therapeutic targets
Han, S., Liu, Y., Cai, S. J., Qian, M., Ding, J., Larion, M., Gilbert, M. R., & Yang, C. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0814-x · Cited by 661 · see citing works
Self-citationCancer cell metabolism: the essential role of the nonessential amino acid, glutamine
Zhang, J., Pavlova, N. N., & Thompson, C. B. (2017) · The EMBO Journal · doi:10.15252/embj.201696151 · Cited by 651 · see citing works
IDH1 and IDH2 mutations in gliomas
Cohen, A. L., Holmen, S. L., & Colman, H. (2013) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-013-0345-4 · Cited by 629 · see citing works
The metabolite alpha-ketoglutarate extends lifespan by inhibiting the ATP synthase and TOR
Chin, R., Fu, X., Pai, M. Y., Vergnes, L., Hwang, H., Deng, G., Diep, S., Lomenick, B., Meli, V., Monsalve, G. C., et al. (2014) · Nature · doi:10.1038/nature13264 · Cited by 570 · see citing works
Yang, H., Liu, Y., Bai, F., Zhang, J., Ma, S.-H., Liu, J., Xu, Z.-D., Zhu, H.-G., Ling, Z.-Q., Ye, D., et al. (2012) · Oncogene · doi:10.1038/onc.2012.67 · Cited by 575 · see citing works
Self-citationWhat a difference a hydroxyl makes: mutant IDH, (<i>R</i>)-2-hydroxyglutarate, and cancer
Losman, J.-A., & Kaelin, W. G. (2013) · Genes & Development · doi:10.1101/gad.217406.113 · Cited by 570 · see citing works
Emerging insights into the molecular and cellular basis of glioblastomaPreprint
Dunn, G. P., Rinne, M. L., Wykosky, J., Genovese, G., Quayle, S. N., Dunn, I. F., Agarwalla, P. K., Chheda, M. G., Campos, B., Wang, A., et al. (2012) · Genes & Development · doi:10.1101/gad.187922.112 · Cited by 559 · see citing works
Reitman, Z. J., & Yan, H. (2010) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djq187 · Cited by 562 · see citing works
Regulation of the pentose phosphate pathway in cancer
Jiang, P., Du, W., & Wu, M. (2014) · Protein & Cell · doi:10.1007/s13238-014-0082-8 · Cited by 568 · see citing works
Anticancer Activity of Metal Complexes: Involvement of Redox Processes
Jungwirth, U., Kowol, C. R., Keppler, B. K., Hartinger, C. G., Berger, W., & Heffeter, P. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3663 · Cited by 559 · see citing works
Tefferi, A. (2010) · Leukemia · doi:10.1038/leu.2010.69 · Cited by 533 · see citing works
Malignant Glioma: Lessons from Genomics, Mouse Models, and Stem Cells
Chen, J., McKay, R. M., & Parada, L. F. (2012) · Cell · doi:10.1016/j.cell.2012.03.009 · Cited by 526 · see citing works
Characterization of R132H Mutation‐specific IDH1 Antibody Binding in Brain Tumors
Capper, D., Weißert, S., Balß, J., Habel, A., Meyer, J., Jaeger, D., Ackermann, U., Tessmer, C., Korshunov, A., Zentgraf, H., et al. (2009) · Brain Pathology · doi:10.1111/j.1750-3639.2009.00352.x · Cited by 523 · see citing works
Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1
Seltzer, M. J., Bennett, B. D., Joshi, A. D., Gao, P., Thomas, A. G., Ferraris, D. V., Tsukamoto, T., Rojas, C. J., Slusher, B. S., Rabinowitz, J. D., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1666 · Cited by 513 · see citing works
IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics
Sasaki, M., Knobbe, C. B., Munger, J. C., Lind, E. F., Brenner, D., Brüstle, A., Harris, I. S., Holmes, R., Wakeham, A., Haight, J., et al. (2012) · Nature · doi:10.1038/nature11323 · Cited by 513 · see citing works
HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells
Mathieu, J., Zhang, Z., Zhou, W., Wang, A. J., Heddleston, J. M., Pinna, C. M. A., Hubaud, A., Stadler, B., Choi, M. P., Bar, M., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3320 · Cited by 510 · see citing works
IDH mutations in cancer and progress toward development of targeted therapeutics
Dang, L., Yen, K., & Attar, E. C. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw013 · Cited by 509 · see citing works
Mitochondrial Dysfunction in Cancer
Boland, M. L., Chourasia, A. H., & Macleod, K. F. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00292 · Cited by 502 · see citing works
BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1
Tönjes, M., Barbus, S., Park, Y. J., Wang, W., Schlotter, M., Lindroth, A. M., Pleier, S. V., Bai, A. H. C., Karra, D., Piro, R. M., et al. (2013) · Nature Medicine · doi:10.1038/nm.3217 · Cited by 486 · see citing works
IDH1andIDH2Mutations in Tumorigenesis: Mechanistic Insights and Clinical Perspectives
Yang, H., Ye, D., Guan, K., & Xiong, Y. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1773 · Cited by 459 · see citing works
Self-citationCarter, H. K., Chen, S., Işık, L., Tyekucheva, S., Velculescu, V. E., Kinzler, K. W., Vogelstein, B., & Karchin, R. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1133 · Cited by 448 · see citing works
Recent advances in the molecular understanding of glioblastoma
Bleeker, F. E., Molenaar, R. J., & Leenstra, S. (2012) · Journal of Neuro-Oncology · doi:10.1007/s11060-011-0793-0 · Cited by 453 · see citing works
Oncogenic Isocitrate Dehydrogenase Mutations: Mechanisms, Models, and Clinical Opportunities
Cairns, R. A., & Mak, T. W. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0083 · Cited by 452 · see citing works
Genetic alterations and signaling pathways in the evolution of gliomas
Ohgaki, H., & Kleihues, P. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01308.x · Cited by 452 · see citing works
Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome
Reitman, Z. J., Jin, G., Karoly, E. D., Spasojevic, I., Yang, J., Kinzler, K. W., He, Y., Bigner, D. D., Vogelstein, B., & Yan, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019393108 · Cited by 449 · see citing works
Monoclonal antibody specific for IDH1 R132H mutation
Capper, D., Zentgraf, H., Balß, J., Hartmann, C. J., & von Deimling, A. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0595-z · Cited by 433 · see citing works
Extreme vulnerability of IDH1 mutant cancers to NAD+ depletion
Tateishi, K., Wakimoto, H., Iafrate, A. J., Tanaka, S., Loebel, F., Lelic, N., Wiederschain, D., Bedel, O., Deng, G., Zhang, B., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.11.006 · Cited by 433 · see citing works
Oncometabolites: linking altered metabolism with cancer
Yang, M. H., Soga, T., & Pollard, P. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67228 · Cited by 424 · see citing works
Dhup, S., Dadhich, R. K., Porporato, P. E., & Sonveaux, P. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799504902 · Cited by 419 · see citing works
Leukemia Stem Cells and Microenvironment: Biology and Therapeutic Targeting
Konopleva, M. Y., & Jordan, C. T. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.31.0904 · Cited by 401 · see citing works
Wang, P., Dong, Q., Zhang, C., Kuan, P.-F., Liu, Y., Jeck, W. R., Andersen, J. B., Jiang, W., Savich, G. L., Tan, T.-X., et al. (2013) · Oncogene · doi:10.1038/onc.2012.315 · Cited by 399 · see citing works
Self-citationCancer cell metabolism: implications for therapeutic targets
Jang, M., Kim, S. S., & Lee, J. (2013) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.85 · Cited by 398 · see citing works
Coupling Krebs cycle metabolites to signalling in immunity and cancer
Ryan, D. G., Murphy, M. P., Frezza, C., Prag, H. A., Chouchani, E. T., O’Neill, L. A., & Mills, E. L. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0014-7 · Cited by 398 · see citing works
Abbas, S., Lugthart, S., Kavelaars, F. G., Schelen, A. M., Koenders, J. E., Zeilemaker, A., van Putten, W. J. L., Rijneveld, A. W., Löwenberg, B., & Valk, P. J. M. (2010) · Blood · doi:10.1182/blood-2009-11-250878 · Cited by 394 · see citing works
The implications of IDH mutations for cancer development and therapy
Pirozzi, C. J., & Yan, H. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00521-0 · Cited by 402 · see citing works
Cancer Development, Progression, and Therapy: An Epigenetic Overview
Sarkar, S., Horn, G., Moulton, K. L., Oza, A. U., Byler, S., Kokolus, S., & Longacre, M. M. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141021087 · Cited by 392 · see citing works
Cancer metabolism: current perspectives and future directions
Muñoz-Pinedo, C., El Mjiyad, N., & Ricci, J.-E. (2012) · Cell Death & Disease · doi:10.1038/cddis.2011.123 · Cited by 385 · see citing works
Miroshnikova, Y. A., Mouw, J. K., Barnes, J. M., Pickup, M. W., Lakins, J. N., Kim, Y., Lobo, K. A., Persson, A. I., Reis, G. F., McKnight, T. R., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3429 · Cited by 380 · see citing works
Singhal, R., & Shah, Y. M. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.011188 · Cited by 379 · see citing works
IDH mutations in glioma and acute myeloid leukemia
Dang, L., Jin, S., & Su, S.-S. M. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.07.002 · Cited by 368 · see citing works
Nutrient Sensing, Metabolism, and Cell Growth Control
Yuan, H.-X., Xiong, Y., & Guan, K. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.019 · Cited by 357 · see citing works
Self-citationPrognostic and Predictive Biomarkers in Gliomas
Śledzińska, P., Bebyn, M. G., Furtak, J., Kowalewski, J., & Lewandowska, M. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910373 · Cited by 347 · see citing works
IDH1 and IDH2 Mutations in Gliomas
Uhm, J. H. (2009) · Yearbook of Neurology and Neurosurgery · doi:10.1016/s0513-5117(09)79085-4 · Cited by 333 · see citing works
Li, Z., Wang, Y., Yu, J., Guo, Y., & Cao, W. (2017) · Scientific Reports · doi:10.1038/s41598-017-05848-2 · Cited by 332 · see citing works
Self-citationReactive Oxygen Species in Cancer Stem Cells
Shi, X., Zhang, Y., Zheng, J., & Pan, J. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4529 · Cited by 326 · see citing works
Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives
Szopa, W., Burley, T. A., Krämer-Marek, G., & Kaspera, W. (2017) · BioMed Research International · doi:10.1155/2017/8013575 · Cited by 321 · see citing works
Tefferi, A., Lasho, T. L., Abdel-Wahab, O. I., Guglielmelli, P., Patel, J. L., Caramazza, D., Pieri, L., Finke, C. M., Kilpivaara, O., Wadleigh, M., et al. (2010) · Leukemia · doi:10.1038/leu.2010.113 · Cited by 317 · see citing works
Kickingereder, P., Sahm, F., Radbruch, A., Wick, W., Heiland, S., von Deimling, A., Bendszus, M., & Wiestler, B. (2015) · Scientific Reports · doi:10.1038/srep16238 · Cited by 314 · see citing works
Bleeker, F. E., Atai, N. A., Lamba, S., Jonker, A., Rijkeboer, D., Bosch, K. S., Tigchelaar, W., Troost, D., Vandertop, W. P., Bardelli, A., et al. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0645-6 · Cited by 304 · see citing works
Carrillo, J., Lai, A., Nghiemphu, P. L., Kim, H. J., PHILLIPS, H. S., Kharbanda, S., Moftakhar, P., Lalaezari, S., Yong, W. H., Ellingson, B. M., et al. (2012) · American Journal of Neuroradiology · doi:10.3174/ajnr.a2950 · Cited by 297 · see citing works
The Redox Basis of Epigenetic Modifications: From Mechanisms to Functional Consequences
Cyr, A. R., & Domann, F. E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3492 · Cited by 294 · see citing works
Cancer-associated IDH mutations: biomarker and therapeutic opportunities
Yen, K. E., Bittinger, M. A., Su, S. M., & Fantin, V. R. (2010) · Oncogene · doi:10.1038/onc.2010.444 · Cited by 296 · see citing works
Sasaki, M., Knobbe, C. B., Itsumi, M., Elia, A. J., Harris, I. S., Chio, I. I. C., Cairns, R. A., McCracken, S., Wakeham, A., Haight, J., et al. (2012) · Genes & Development · doi:10.1101/gad.198200.112 · Cited by 296 · see citing works
Progress in understanding 2‐hydroxyglutaric acidurias
Kranendijk, M., Struys, E. A., Salomons, G. S., Van der Knaap, M. S., & Jakobs, C. (2012) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-012-9462-5 · Cited by 292 · see citing works
Lin, R., Elf, S., Shan, C., Kang, H.-B., Ji, Q., Zhou, L., Hitosugi, T., Zhang, L., Zhang, S., Seo, J. H., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3255 · Cited by 287 · see citing works
Self-citationIsocitrate dehydrogenase mutations in gliomas
Waitkus, M. S., Diplas, B. H., & Yan, H. (2015) · Neuro-Oncology · doi:10.1093/neuonc/nov136 · Cited by 282 · see citing works
Metabolic genes in cancer: Their roles in tumor progression and clinical implications
Furuta, E., Okuda, H., Kobayashi, A., & Watabe, K. (2010) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2010.01.005 · Cited by 283 · see citing works
Molecular diagnostics of gliomas: state of the art
Riemenschneider, M. J., Jeuken, J. W. M., Wesseling, P., & Reifenberger, G. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0736-4 · Cited by 283 · see citing works
Caveolin-1 and Cancer Metabolism in the Tumor Microenvironment: Markers, Models, and Mechanisms
Sotgia, F., Martinez‐Outschoorn, U., Howell, A., Pestell, R. G., Pavlides, S., & Lisanti, M. P. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011811-120856 · Cited by 283 · see citing works
Korshunov, A., Meyer, J., Capper, D., Christians, A., Remke, M., Witt, H., Pfister, S. M., von Deimling, A., & Hartmann, C. J. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0550-z · Cited by 274 · see citing works
Collagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance
Xiong, G., Stewart, R. L., Chen, J., Gao, T., Scott, T. L., Samayoa, L. M., O’Connor, K. L., Lane, A. N., & Xu, R. (2018) · Nature Communications · doi:10.1038/s41467-018-06893-9 · Cited by 277 · see citing works
Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers
Jansen, M., Yip, S. S. F., & Louis, D. N. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70105-8 · Cited by 272 · see citing works
- Authors
- Zhao, S., Lin, Y., Xu, W., Jiang, W., Zha, Z., Wang, P., Yu, W., Li, Z., Gong, L., Peng, Y., Ding, J., Lei, Q., Guan, K.-L., & Xiong, Y.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Molecular and Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, 130 Dong-An Road, Shanghai 200032, China.
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Lin, Yan
- Xu, Wei
- Jiang, Wenqing
- Guan, Kun-Liang
- Xiong, Yue
- ORCID
- Venue
- Science
- Published
- 2009-04-10
- Volume
- 324
- Issue
- 5924
- Pages
- 261-265
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3251015
- OpenAlex
- W1964150693
- Cited by
- 1,119
- References
- 12
- Citations by year
- 2026: 24 · 2025: 27 · 2024: 43 · 2023: 36 · 2022: 50 · 2021: 62 · 2020: 58 · 2019: 54 · 2018: 63 · 2017: 71 · 2016: 57 · 2015: 71 · 2014: 74 · 2013: 90 · 2012: 84
- FWCI
- 37.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA068377)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- IDH1 mutation, isocitrate dehydrogenase, glioma, HIF-1α, alpha-ketoglutarate, heterodimer formation, tumor suppressor, hypoxia, carcinogenesis, brain tumors, enzyme activity
- MeSH terms
- Adolescent, Adult, Aged, Astrocytoma, Brain Neoplasms, Cell Line, Child, Female, Glioblastoma, Glioma, Humans, Isocitrate Dehydrogenase, Ketoglutaric Acids, Male, Middle Aged, Oligodendroglioma, Oxalates, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Mutant Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Biocatalysis, Protein Multimerization
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