Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases
Open accessAbstract
IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as α-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased levels of 2-HG may enable a switch to an entirely HIF-independent mechanism.
“Therefore, it is plausible that increased levels of 2-HG may enable a switch to an entirely HIF-independent mechanism.”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [152]
The Discussion section ‘IDH1 and IDH2 Mutations Alter Histone and DNA Methylation’ (page unavailable) proposes that 2-HG-related epigenetic changes may contribute to tumorigenesis, supporting a possible mechanism beyond HIF. But the Results section ‘2-HG Treatment Inhibits PHD and C-P4H’ reports that 2-HG also increases HIF-1α; the paper does not describe a switch to an entirely HIF-independent mechanism. (LLM, conf=0.84)
Experimental — accuracy not yet measured2-hydroxyglutarate interferes with iron-dependent hydroxylases, including the TET family of 5-methylcytosine hydroxylases.
“Mutant IDH protein produces a novel onco-metabolite, 2-hydroxyglutarate (2-HG), that interferes with iron-dependent hydroxylases, including the TET family of 5′-methylcytosine hydroxylases3–7.”
From Insulator dysfunction and oncogene activation in IDH mutant gliomas (2016) · cites this paper as [5]
Mutant IDH protein generates the oncometabolite 2-hydroxyglutarate.
“Mutant IDH protein produces a novel onco-metabolite, 2-hydroxyglutarate (2-HG), that interferes with iron-dependent hydroxylases, including the TET family of 5′-methylcytosine hydroxylases3–7.”
From Insulator dysfunction and oncogene activation in IDH mutant gliomas (2016) · cites this paper as [5]
The observation that IDH1 and IDH2 mutations can partially phenocopy the loss of TET function may explain the mutual exclusivity of these mutations in cancer.
“The observation that IDH1 and IDH2 mutations can partially phenocopy the loss of TET function may explain the mutual exclusivity of these mutations in cancer 95,97 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [97]
The mutant IDH enzyme competitively blocks hydroxylases, among them TET enzymes that hydroxylate 5mC.
“Mutant IDH protein is a competitive inhibitor of hydroxylases, including the TET family of 5mC hydroxylases120–122.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [122]
PU.1 guides TET2 to a specific subset of genomic regions to facilitate the oxidation of 5mC to 5hmC, a reaction inhibited by 2-hydroxyglutarate and enhanced by vitamin C.
“These observations support a model in which PU.1 guides TET2 to a specific subset of genomic regions to facilitate the oxidation of 5mC to 5hmC, a reaction that is inhibited by 2-hydroxyglutarate47 and enhanced by vitamin C13 (Figure 5d).”
From Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia (2018) · cites this paper as [47]
In the cancer setting, 2-HG influences a number of biological processes, including cell differentiation, DNA methylation, and histone methylation.
“In the cancer setting, 2-HG has been shown to influence a number of biological processes, including cell differentiation, DNA methylation, and histone methylation (79–82), leading to its classification as an oncometabolite.”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [81]
2-HG acts as a competitive inhibitor of α-KG, and its production by mutant IDH1 consumes α-KG, leading to reduced TET2 and JmjC activity in tumor cells.
“For example, 2-HG acts as a competitive inhibitor of α-KG, and its production by mutant IDH1 consumes α-KG (81, 99), leading to reduced TET2 and JmjC activity in tumor cells (79, 80).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [81]
TH17 cell differentiation can be initiated by exogenous addition of D-2-HG to naïve CD4+ T cells or by genetic silencing of TET1 and TET2.
“Furthermore, TH17 cell differentiation could be initiated by exogenous addition of D-2-HG to naïve CD4+ T cells or by genetic silencing of TET1 and TET2, established targets of 2-HG143-145.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [145]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.020 · Cited by 7,575 · see citing works
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
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836 · see citing works
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535 · see citing works
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 2× · see citing works
“HIF-1a is a transcription factor whose function is linked to metabolism, angiogenesis and tumorigenesis, and whose protein level is downregulated under normoxic conditions by PHD-mediated hydroxylation and subsequent hydroxylation-targeted ubiquitination (Bruick and McKnight, 2001; Epstein et al., 2001; Ivan et al., 2…”
Self-citationEndostatin: an endogenous inhibitor of angiogenesis and tumor growth
O'Reilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W. S., Flynn, E., Birkhead, J. R., Olsen, B. R., & Folkman, J. (1997) · Cell · doi:10.1016/s0092-8674(00)81848-6 · Cited by 4,486 · 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
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333 · see citing works
Figueroa, M. E., Abdel-Wahab, O., Lu, C., Ward, P. S., Patel, J., Shih, A., Li, Y., Bhagwat, N., Vasanthakumar, A., Fernandez, H. F., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.015 · Cited by 2,766 · see citing works
The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Kriaucionis, S., & Heintz, N. (2009) · Science · doi:10.1126/science.1169786 · Cited by 2,700 · see citing works
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549 · see citing works
Ito, S., D’Alessio, A. C., Taranova, O., Hong, K., Sowers, L. C., & Zhang, Y. (2010) · Nature · doi:10.1038/nature09303 · Cited by 2,542 · see citing works
Self-citationIdentification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma
Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelloski, C. E., Sulman, E. P., Bhat, K. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.03.017 · Cited by 2,337 · 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
Histone demethylation by a family of JmjC domain-containing proteins
Tsukada, Y.-I., Fang, J., Erdjument‐Bromage, H., Warren, M., Borchers, C. H., Tempst, P., & Zhang, Y. (2005) · Nature · doi:10.1038/nature04433 · Cited by 2,171 · see citing works
Self-citationSuccinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
Selak, M. A., Armour, S. M., MacKenzie, E. D., Boulahbel, H., Watson, D. G., Mansfield, K. D., Pan, Y., Simon, M. C., Thompson, C. B., & Gottlieb, E. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.11.022 · Cited by 2,108 · cited 1× · see citing works
“Mutations targeting FH and SDH lead to similar increase in the PHD substrate, HIF-1a (Isaacs et al., 2005; Pollard et al., 2005; Selak et al., 2005).”
BackgroundWard, 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 · cited 7× · see citing works
“Recently, it was reported that expression of IDH1R132H suppresses TET2 activity and the mutations of IDH1 and IDH2 genes occur in a mutual exclusive manner with that of TET2 gene in AML (Figueroa et al., 2010).”
InfluentialMutation in <i>TET2</i> in Myeloid Cancers
Delhommeau, F., Dupont, S., Valle, V. D., James, C., Trannoy, S., Massé, A., Kosmider, O., Le Couedic, J.-P., Robert, F., Alberdi, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810069 · Cited by 1,776 · see citing works
Mutations in <i>SDHD</i> , a Mitochondrial Complex II Gene, in Hereditary Paraganglioma
Baysal, B. E., Ferrell, R. E., Willett-Brozick, J. E., Lawrence, E. C., Myssiorek, D., Bosch, A., Mey, A. V. D., Taschner, P. E. M., Rubinstein, W. S., Myers, E. N., et al. (2000) · Science · doi:10.1126/science.287.5454.848 · Cited by 1,638 · see citing works
The Multiple Leiomyoma Consortium (2002) · Nature Genetics · doi:10.1038/ng849 · Cited by 1,635 · see citing works
Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550 · cited 2× · see citing works
“In addition to PHDs, the stability and steady-state levels of HIF-1a protein are also regulated by FIH-1 (factor inhibiting HIF-1a) (Lando et al., 2002; Mahon et al., 2001), an asparaginyl hydrogenase whose activity is dependent on a-KG and could therefore also be affected by reduced function of IDH1.”
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385 · see citing works
Glioma-Derived Mutations in <i>IDH1</i> Dominantly Inhibit IDH1 Catalytic Activity and Induce HIF-1α
Zhao, S., Lin, Y., Xu, W., Jiang, W., Zha, Z., Wang, P., Yu, W., Li, Z., Gong, L., Peng, Y., et al. (2009) · Science · doi:10.1126/science.1170944 · Cited by 1,119 · see citing works
Self-citationGao, X., Wu, G., Gu, X., Fu, L., & Mei, C. (2013) · Kidney & Blood Pressure Research · doi:10.1159/000355743 · Cited by 1,036 · see citing works
IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas
Watanabe, T., Nobusawa, S., Kleihues, P., & Ohgaki, H. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080958 · Cited by 1,027 · see citing works
Isaacs, J. S., Jung, Y. J., Mole, D. R., Lee, S., Torres-Cabala, C., Chung, Y.-L., Merino, M., Trepel, J., Zbar, B., Toro, J., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.06.017 · Cited by 958 · see citing works
Pollard, P. J., Brière, J. J., Alam, N. A., Barwell, J., Barclay, E., Wortham, N. C., Hunt, T., Mitchell, M., Olpin, S., Moat, S. J., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi227 · Cited by 865 · see citing works
Acquired mutations in TET2 are common in myelodysplastic syndromes
Langemeijer, S. M. C., Kuiper, R. P., Berends, M., Knops, R., Aslanyan, M. G., Massop, M., Stevens-Linders, E., van Hoogen, P., van Kessel, A. G., Raymakers, R. A. P., et al. (2009) · Nature Genetics · doi:10.1038/ng.391 · Cited by 755 · 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
H3K79 methylation profiles define murine and human MLL-AF4 leukemias
Krivtsov, A., Feng, Z.-H., Lemieux, M., Faber, J., Vempati, S., Sinha, A., Xia, X.-B., Jesneck, J., Bracken, A., Silverman, L., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.10.001 · Cited by 573 · see citing works
Expanding chemical biology of 2-oxoglutarate oxygenases
Loenarz, C., & Schofield, C. J. (2008) · Nature Chemical Biology · doi:10.1038/nchembio0308-152 · Cited by 498 · see citing works
Yamane, K., Tateishi, K., Klose, R. J., Fang, J., Fabrizio, L. A., Erdjument‐Bromage, H., Taylor‐Papadimitriou, J., Tempst, P., & Zhang, Y. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.03.001 · Cited by 493 · see citing works
Self-citationStructural studies on 2-oxoglutarate oxygenases and related double-stranded β-helix fold proteins
Clifton, I. J., McDonough, M. A., Ehrismann, D., Kershaw, N. J., Granatino, N., & Schofield, C. J. (2006) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2006.01.024 · Cited by 444 · see citing works
Lorsbach, R. B., Moore, J., Mathew, S., Raimondi, S. C., Mukatira, S. T., & Downing, J. R. (2003) · Leukemia · doi:10.1038/sj.leu.2402834 · Cited by 416 · see citing works
Iyer, L. M., Tahiliani, M., Rao, A., & Aravind, L. (2009) · Cell Cycle · doi:10.4161/cc.8.11.8580 · Cited by 397 · see citing works
Structural Insights into Histone Demethylation by JMJD2 Family Members
Chen, Z., Zang, J., Whetstine, J. R., Hong, X., Davrazou, F., Kutateladze, T. G., Simpson, M., Mao, Q., Pan, C., Dai, S., et al. (2006) · Cell · doi:10.1016/j.cell.2006.04.024 · Cited by 396 · see citing works
JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer
Xiang, Y., Zhu, Z., Han, G., Ye, X., Xu, B., Peng, Z., Ma, Y., Yu, Y., Lin, H., Chen, A. P., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700735104 · Cited by 395 · see citing works
Quantification of the Sixth DNA Base Hydroxymethylcytosine in the Brain
Münzel, M., Globisch, D., Brückl, T., Wagner, M., Welzmiller, V., Michalakis, S., Müller, M., Biel, M., & Carell, T. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201002033 · Cited by 390 · see citing works
Ono, R., Taki, T., Taketani, T., Taniwaki, M., Kobayashi, H., & Hayashi, Y. (2002) · PubMed · Cited by 278 · see citing works
Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase
Couture, J., Collazo, E., Ortiz-Tello, P. A., Brunzelle, J. S., & Trievel, R. C. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1273 · Cited by 276 · see citing works
The Asparaginyl Hydroxylase Factor Inhibiting HIF-1α Is an Essential Regulator of Metabolism
Zhang, N., Fu, Z., Linke, S., Chicher, J., Gorman, J. J., Visk, D., Haddad, G. G., Poellinger, L., Peet, D. J., Powell, F. L., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.001 · Cited by 244 · see citing works
Lu, P., Sundquist, K., Baeckström, D., Poulsom, R., Hanby, A. M., Meier‐Ewert, S., Jones, T. A., Mitchell, M., Pitha-Rowe, P. M., Freemont, P. S., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.22.15633 · Cited by 231 · see citing works
Rzem, R., Veiga-da-Cunha, M., Noël, G., Goffette, S., Nassogne, M.-C., Tabarki, B., Schöller, C., Marquardt, T., Vikkula, M., & Van Schaftingen, E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404840101 · Cited by 195 · see citing works
Succinate inhibition of α-ketoglutarate-dependent enzymes in a yeast model of paraganglioma
Smith, E. H., Janknecht, R., & Maher, L. J. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm275 · Cited by 169 · see citing works
Hydroxyglutaric aciduria and malignant brain tumor: a case report and literature review
Aghili, M., Zahedi, F., & Rafiee, E. (2009) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9706-2 · Cited by 159 · see citing works
Krane, S. M. (2008) · Amino Acids · doi:10.1007/s00726-008-0073-2 · Cited by 156 · see citing works
Topçu, M., Jobard, F., Halliez, S., Coskun, T., Yalçinkayal, C., Gerceker, F. O., Wanders, R. J. A., Prud'homme, J.-F., Lathrop, M., Özguc, M., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh300 · Cited by 133 · see citing works
Yang, B., Zhong, C., Peng, Y., Lai, Z., & Ding, J. (2010) · Cell Research · doi:10.1038/cr.2010.145 · Cited by 118 · see citing works
Cunliffe, C. J., Franklin, T. J., Hales, N. J., & Hill, G. B. (1992) · Journal of Medicinal Chemistry · doi:10.1021/jm00092a016 · Cited by 94 · see citing works
Бей, Yang, Chen, Zhong, Yingjie, ......................................................, P., Zheng, Lai, Jianping, & Ding (2010) · Acta Scientiarum Naturalium Universitatis Sunyatseni · Cited by 67 · see citing works
Simmons, J. M., Müller, T., & Hausinger, R. P. (2008) · Dalton Transactions · doi:10.1039/b803512a · Cited by 60 · see citing works
Diagnostic and prognostic markers in gliomas
Ducray, F., Hallani, S. E., & Idbaïh, A. (2009) · Current Opinion in Oncology · doi:10.1097/cco.0b013e32833065a7 · Cited by 47 · see citing works
Novel inhibitors of prolyl 4-hydroxylase
Dowell, R. I., & Hadley, E. M. (1992) · Journal of Medicinal Chemistry · doi:10.1021/jm00083a001 · Cited by 40 · see citing works
Flagged first, then by citations
1 of the 55 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · 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
Cancer epigenetics: from mechanism to therapy
Dawson, M. A., & Kouzarides, T. (2012) · Cell · doi:10.1016/j.cell.2012.06.013 · Cited by 3,203 · see citing works
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013 · see citing works
Mitochondrial TCA cycle metabolites control physiology and disease
Martínez-Reyes, I., & Chandel, N. S. (2020) · Nature Communications · doi:10.1038/s41467-019-13668-3 · Cited by 2,813 · see citing works
IDH mutation impairs histone demethylation and results in a block to cell differentiation
Lu, C., Ward, P. S., Kapoor, G. S., Rohle, D., Turcan, S., Abdel-Wahab, O., Edwards, C. R., Khanin, R., Figueroa, M. E., Melnick, A., et al. (2012) · Nature · doi:10.1038/nature10860 · Cited by 1,985 · see citing works
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype
Turcan, S., Rohle, D., Goenka, A., Walsh, L. A., Fang, F., Yilmaz, E., Campos, C., Fabius, A. W. M., Lu, C., Ward, P. S., et al. (2012) · Nature · doi:10.1038/nature10866 · Cited by 1,974 · see citing works
Sturm, D., Witt, H., Hovestadt, V., Khuong-Quang, D.-A., Jones, D. T. W., Konermann, C., Pfaff, E., Tönjes, M., Sill, M., Bender, S., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.08.024 · Cited by 1,828 · see citing works
TET-mediated active DNA demethylation: mechanism, function and beyond
Wu, X., & Zhang, Y. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.33 · Cited by 1,661 · see citing works
Self-citationTET enzymes, TDG and the dynamics of DNA demethylation
Kohli, R. M., & Zhang, Y. (2013) · Nature · doi:10.1038/nature12750 · Cited by 1,623 · see citing works
Self-citationEnasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia
Stein, E. M., DiNardo, C. D., Pollyea, D. A., Fathi, A. T., Roboz, G. J., Altman, J. K., Stone, R. M., DeAngelo, D. J., Levine, R. L., Flinn, I. W., et al. (2017) · Blood · doi:10.1182/blood-2017-04-779405 · Cited by 1,516 · see citing works
Durable Remissions with Ivosidenib in IDH1 -Mutated Relapsed or Refractory AML
Dinardo, C. D., Stein, E. M., de Botton, S., Roboz, G. J., Altman, J. K., Mims, A. S., Swords, R. T., Collins, R. H., Mannis, G. N., Pollyea, D. A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716984 · Cited by 1,468 · see citing works
Self-citationTargeting cancer metabolism: a therapeutic window opens
Heiden, M. G. V. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3504 · Cited by 1,409 · see citing works
Insulator dysfunction and oncogene activation in IDH mutant gliomas
Flavahan, W. A., Drier, Y., Liau, B. B., Gillespie, S. M., Venteicher, A. S., Stemmer-Rachamimov, A. O., Suvà, M. L., & Bernstein, B. E. (2016) · Nature · doi:10.1038/nature16490 · Cited by 1,288 · see citing works
Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult Brain
Guo, J. U., Su, Y., Zhong, C., Ming, G., & Song, H. (2011) · Cell · doi:10.1016/j.cell.2011.03.022 · Cited by 1,355 · see citing works
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363 · see citing works
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation
Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.001 · Cited by 1,339 · see citing works
Lessons from the Cancer Genome
Garraway, L. A., & Lander, E. S. (2013) · Cell · doi:10.1016/j.cell.2013.03.002 · Cited by 1,322 · see citing works
Histone Lysine Methylation Dynamics: Establishment, Regulation, and Biological Impact
Black, J. C., Rechem, C. V., & Whetstine, J. R. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.11.006 · Cited by 1,325 · see citing works
Mitochondrial metabolism and cancer
Porporato, P. E., Filigheddu, N., Pedro, J. M. B., Kroemer, G., & Galluzzi, L. (2017) · Cell Research · doi:10.1038/cr.2017.155 · Cited by 1,292 · see citing works
Writing, erasing and reading histone lysine methylations
Hyun, K., Jeon, J., Park, K., & Kim, J. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.11 · Cited by 1,250 · see citing works
Metabolomics for Investigating Physiological and Pathophysiological Processes
Wishart, D. S. (2019) · Physiological Reviews · doi:10.1152/physrev.00035.2018 · Cited by 1,246 · see citing works
Editing DNA Methylation in the Mammalian Genome
Liu, X. S., Wu, H., Ji, X., Stelzer, Y., Wu, X., Czauderna, S., Shu, J., Dadon, D., Young, R. A., & Jaenisch, R. (2016) · Cell · doi:10.1016/j.cell.2016.08.056 · Cited by 1,224 · 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
“…mutated IDH1 and IDH2 inhibits the activity of a-KG-dependent dioxygenases and, more importantly, produces 2-HG, which acts as an antagonist of a-KG to competitively inhibit the activity of a-KG-dependent dioxygenases, including both KDMs and TETs (Chowdhury et al. 2011; Xu et al. 2011).”
BackgroundSelf-citationAn inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells
Rohle, D., Popovici-Muller, J., Palaskas, N., Turcan, S., Grommes, C., Campos, C., Tsoi, J., Clark, O., Oldrini, B., Komisopoulou, E., et al. (2013) · Science · doi:10.1126/science.1236062 · Cited by 1,153 · see citing works
Self-citationCairncross, G. J., Wang, M., Shaw, E., Jenkins, R. B., Brachman, D. G., Buckner, J. C., Fink, K., Souhami, L., Laperrière, N., Curran, W., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.2674 · Cited by 1,152 · see citing works
R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling
Su, R., Dong, L., Li, C., Nachtergaele, S., Wunderlich, M., Qing, Y., Deng, X., Wang, Y., Weng, X., Hu, C., et al. (2018) · Cell · doi:10.1016/j.cell.2017.11.031 · Cited by 1,137 · see citing works
“Because IDH mutants block cell differentiation and promote tumor transformation, and inhibition of mutant IDH (IDHi) can reverse this effect, R-2HG (as the major metabolic product of IDH mutants) has been regarded as an oncometabolite (Figueroa et al., 2010; Lu et al., 2012; Rohle et al., 2013;Wang et al., 2013; Xu et…”
BackgroundWeller, M., Wick, W., Aldape, K. D., Brada, M., Berger, M. S., Pfister, S. M., Nishikawa, R., Rosenthal, M. A., Wen, P. Y., Stupp, R., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.17 · Cited by 1,129 · see citing works
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions
Wu, H., & Zhang, Y. (2014) · Cell · doi:10.1016/j.cell.2013.12.019 · Cited by 1,065 · see citing works
Self-citationRole of TET enzymes in DNA methylation, development, and cancer
Rasmussen, K. D., & Helin, K. (2016) · Genes & Development · doi:10.1101/gad.276568.115 · Cited by 1,040 · see citing works
Links between metabolism and cancerPreprint
Dang, C. V. (2012) · Genes & Development · doi:10.1101/gad.189365.112 · Cited by 991 · see citing works
Donohoe, D. R., Collins, L. B., Wali, A., Bigler, R., Sun, W., & Bultman, S. J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.033 · Cited by 993 · see citing works
Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives
Spruijt, C. G., Gnerlich, F., Smits, A. H., Pfaffeneder, T., Jansen, P. W. T. C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., et al. (2013) · Cell · doi:10.1016/j.cell.2013.02.004 · Cited by 973 · see citing works
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971 · see citing works
Cancer Cell Metabolism: One Hallmark, Many Faces
Cantor, J. R., & Sabatini, D. M. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0345 · Cited by 945 · 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
Influence of Metabolism on Epigenetics and Disease
Kaelin, W. G., & McKnight, S. L. (2013) · Cell · doi:10.1016/j.cell.2013.03.004 · Cited by 920 · see citing works
Cancer Epigenetics: Tumor Heterogeneity, Plasticity of Stem-like States, and Drug Resistance
Easwaran, H., Tsai, H.-C., & Baylin, S. B. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.015 · Cited by 915 · see citing works
Interplay between the Cancer Genome and Epigenome
Shen, H., & Laird, P. W. (2013) · Cell · doi:10.1016/j.cell.2013.03.008 · Cited by 912 · see citing works
Glutaminolysis: A Hallmark of Cancer Metabolism
Yang, L., Venneti, S., & Nagrath, D. (2017) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071516-044546 · Cited by 859 · see citing works
Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us?
DeBerardinis, R. J., & Thompson, C. B. (2012) · Cell · doi:10.1016/j.cell.2012.02.032 · Cited by 858 · 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
5-hmC–mediated epigenetic dynamics during postnatal neurodevelopment and aging
Szulwach, K. E., Li, X., Li, Y., Song, C., Wu, H., Dai, Q., Irier, H. A., Upadhyay, A. K., Gearing, M., Levey, A. I., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2959 · Cited by 819 · see citing works
Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma
Mellinghoff, I. K., van den Bent, M. J., Blumenthal, D. T., Touat, M., Peters, K. B., Clarke, J., Mendez, J., Yust-Katz, S., Welsh, L., Mason, W. P., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2304194 · Cited by 814 · see citing works
Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation
Wang, F., Travins, J., DeLaBarre, B., Penard-Lacronique, V., Schalm, S., Hansen, E., Straley, K., Kernytsky, A., Liu, W., Gliser, C., et al. (2013) · Science · doi:10.1126/science.1234769 · Cited by 804 · see citing works
Self-citationSDH mutations establish a hypermethylator phenotype in paraganglioma
Letouzé, E., Martinelli, C., Loriot, C., Burnichon, N., Abermil, N., Ottolenghi, C., Janin, M., Menara, M., Nguyen, A. T., Benit, P., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.04.018 · Cited by 776 · see citing works
Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma
Lian, C. G., Xu, Y., Ceol, C., Wu, F., Larson, A., Dresser, K., Xu, W., Tan, L., Hu, Y., Zhan, Q., et al. (2012) · Cell · doi:10.1016/j.cell.2012.07.033 · Cited by 789 · see citing works
Self-citationTumor biomarkers for diagnosis, prognosis and targeted therapy
Zhou, Y., Tao, L., Qiu, J., Xu, J., Yang, X., Zhang, Y., Tian, X., Guan, X., Cen, X., & Zhao, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01823-2 · Cited by 772 · see citing works
Self-citationBorger, 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
Neinast, M. D., Murashige, D., & Arany, Z. P. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114455 · 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
Transcription factors as readers and effectors of DNA methylation
Zhu, H., Wang, G., & Qian, J. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.83 · Cited by 649 · see citing works
Losman, J.-A., Looper, R. E., Koivunen, P., Lee, S., Schneider, R. K., McMahon, C., Cowley, G. S., Root, D. E., Ebert, B. L., & Kaelin, W. G. (2013) · Science · doi:10.1126/science.1231677 · Cited by 703 · see citing works
Metabolic Regulation of Epigenetics
Lu, C., & Thompson, C. B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.001 · Cited by 699 · see citing works
The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia
Sperling, A. S., Gibson, C. J., & Ebert, B. L. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.112 · Cited by 676 · see citing works
The role of mutations in epigenetic regulators in myeloid malignancies
Shih, A. H., Abdel-Wahab, O. I., Patel, J. P., & Levine, R. L. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3343 · Cited by 671 · see citing works
Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidationPreprint
Wu, H., & Zhang, Y. (2011) · Genes & Development · doi:10.17615/800j-yk16 · Cited by 665 · see citing works
Self-citationIDH 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-citationAdvances in the molecular genetics of gliomas — implications for classification and therapy
Reifenberger, G., Wirsching, H.-G., Knobbe-Thomsen, C. B., & Weller, M. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.204 · Cited by 662 · see citing works
Metabolomics in cancer research and emerging applications in clinical oncology
Schmidt, D. R., Patel, R., Kirsch, D. G., Lewis, C. A., Heiden, M. G. V., & Locasale, J. W. (2021) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21670 · Cited by 652 · see citing works
Tumour hypoxia causes DNA hypermethylation by reducing TET activity
Thienpont, B., Steinbacher, J., Zhao, H., D’Anna, F., Kuchnio, A., Ploumakis, A., Ghesquière, B., Van Dyck, L., Boeckx, B., Schoonjans, L., et al. (2016) · Nature · doi:10.1038/nature19081 · Cited by 635 · 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
Weller, M., Wen, P. Y., Chang, S. M., Dirven, L., Lim, M. K., Monje, M., & Reifenberger, G. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00516-y · Cited by 645 · see citing works
Ko, M., Bandukwala, H. S., An, J., Lamperti, E. D., Thompson, E. C., Hastie, R., Tsangaratou, A., Rajewsky, K., Koralov, S. B., & Rao, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112317108 · Cited by 616 · see citing works
Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles
Farshidfar, F., Zheng, S., Gingras, M., Newton, Y., Shih, J., Robertson, A. G., Hinoue, T., Hoadley, K. A., Gibb, E. A., Roszik, J., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.02.033 · Cited by 611 · 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
The diverse functions of Dot1 and H3K79 methylationPreprint
Nguyen, A. T., & Zhang, Y. (2011) · Genes & Development · doi:10.1101/gad.2057811 · Cited by 602 · see citing works
Self-citationMGMT testing—the challenges for biomarker-based glioma treatment
Wick, W., Weller, M., van den Bent, M. J., Sanson, M., Weiler, M., von Deimling, A., Plass, C., Hegi, M. E., Platten, M., & Reifenberger, G. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.100 · Cited by 580 · see citing works
The hallmarks of cancer immune evasion
Galassi, C., Chan, T. A.-T., Vitale, I., & Galluzzi, L. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.09.010 · Cited by 595 · see citing works
Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia
Chan, S. M., Thomas, D., Corces, M. R., Xavy, S., Rastogi, S., Hong, W., Zhao, F., Medeiros, B. C., Tyvoll, D. A., & Majeti, R. (2015) · Nature Medicine · doi:10.1038/nm.3788 · Cited by 580 · 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
Sulkowski, P. L., Corso, C. D., Robinson, N. D., Scanlon, S. E., Purshouse, K. R., Bai, H., Liu, Y., Sundaram, R. K., Hegan, D. C., Fons, N. R., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal2463 · Cited by 556 · see citing works
Self-citationThe emerging role and targetability of the TCA cycle in cancer metabolism
Anderson, N. M., Mucka, P., Kern, J. G., & Feng, H. (2017) · Protein & Cell · doi:10.1007/s13238-017-0451-1 · Cited by 558 · see citing works
Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge
Sturm, D., Bender, S., Jones, D. T. W., Lichter, P., Grill, J., Becher, O., Hawkins, C., Majewski, J., Jones, C., Costello, J. F., et al. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3655 · Cited by 555 · see citing works
The roles of DNA, RNA and histone methylation in ageing and cancer
Michalak, E. M., Burr, M. L., Bannister, A. J., & Dawson, M. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0143-1 · Cited by 549 · see citing works
Glioma epigenetics: From subclassification to novel treatment options
Gusyatiner, O., & Hegi, M. E. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.11.010 · Cited by 547 · see citing works
Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate
Bunse, L., Pusch, S., Bunse, T., Sahm, F., Sanghvi, K., Friedrich, M., Alansary, D., Sonner, J. K., Green, E., Deumelandt, K., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0095-6 · Cited by 544 · see citing works
Altered metabolism in cancer: insights into energy pathways and therapeutic targets
Tufail, M., Jiang, C.-H., & Li, N. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02119-3 · Cited by 534 · see citing works
Mitochondrial DNA copy number variation across human cancers
Reznik, E., Miller, M. L., Şenbabaoğlu, Y., Riaz, N., Sarungbam, J., Tickoo, S. K., Al‐Ahmadie, H. A., Lee, W., Seshan, V., Hakimi, A. A., et al. (2016) · eLife · doi:10.7554/elife.10769 · Cited by 515 · 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
The landscape of cancer cell line metabolism
Li, H., Ning, S., Ghandi, M., Kryukov, G. V., Gopal, S., Deik, A., Souza, A., Pierce, K. A., Keskula, P., Hernandez, D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0404-8 · Cited by 511 · see citing works
Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes
Etchegaray, J., & Mostoslavsky, R. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.029 · Cited by 521 · see citing works
Glucose transporters in cancer – from tumor cells to the tumor microenvironment
Ancey, P., Contat, C., & Meylan, E. (2018) · FEBS Journal · doi:10.1111/febs.14577 · Cited by 516 · see citing works
Hypoxia Induces Production of L-2-Hydroxyglutarate
Intlekofer, A. M., Dematteo, R. G., Venneti, S., Finley, L. W. S., Lu, C., Judkins, A. R., Rustenburg, A. S., Grinaway, P. B., Chodera, J. D., Cross, J. R., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.06.023 · 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
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
UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells
Zhang, J., Khvorostov, I., Hong, J. S., Oktay, Y., Vergnes, L., Nuebel, E., Wahjudi, P. N., Setoguchi, K., Wang, G., Do, A., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.401 · Cited by 499 · see citing works
Self-citationMitochondrial 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
Chan-on, W., Nairismägi, M., Ong, C. K., Lim, W. K., Dima, S., Pairojkul, C., Lim, K. H., McPherson, J. R., Cutcutache, I., Heng, H. L., et al. (2013) · Nature Genetics · doi:10.1038/ng.2806 · Cited by 495 · see citing works
Mitochondrial complex III is essential for suppressive function of regulatory T cells
Weinberg, S. E., Singer, B. D., Steinert, E. M., Martinez, C. A., Mehta, M., Martínez‐Reyes, I., Gao, P., Helmin, K. A., Abdala‐Valencia, H., Sena, L. A., et al. (2019) · Nature · doi:10.1038/s41586-018-0846-z · Cited by 496 · see citing works
2-Oxoglutarate-Dependent Oxygenases
Islam, M. S., Leissing, T. M., Chowdhury, R., Hopkinson, R. J., & Schofield, C. J. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044724 · Cited by 472 · 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
Cancer epigenetics: Moving forward
Nebbioso, A., Tambaro, F. P., Dell’Aversana, C., & Altucci, L. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007362 · Cited by 481 · see citing works
Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer
Wu, D., Hu, D., Chen, H., Shi, G., Fetahu, I. S., Wu, F., Rabidou, K., Fang, R., Tan, L., Xu, S., et al. (2018) · Nature · doi:10.1038/s41586-018-0350-5 · Cited by 477 · see citing works
Self-citationMitochondria as Signaling Organelles Control Mammalian Stem Cell Fate
Chakrabarty, R. P., & Chandel, N. S. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.02.011 · Cited by 490 · see citing works
Metabolic Regulation in Pluripotent Stem Cells during Reprogramming and Self-Renewal
Zhang, J., Nuebel, E., Daley, G. Q., Koehler, C. M., & Teitell, M. A. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.10.005 · Cited by 465 · see citing works
Self-citation
- Authors
- Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., Liu, L.-X., Jiang, W.-Q., Liu, J., Zhang, J.-Y., Wang, B., Frye, S., Zhang, Y., Xu, Y.-H., Lei, Q.-Y., Guan, K.-L., Zhao, S.-M., & Xiong, Y.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- University of North Carolina at Chapel Hill (US)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Guan, Kun-Liang
- Xiong, Yue
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 19
- Issue
- 1
- Pages
- 17-30
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3229304
- OpenAlex
- W2131860315
- Cited by
- 2,875
- References
- 55
- Citations by year
- 2026: 165 · 2025: 168 · 2024: 192 · 2023: 182 · 2022: 183 · 2021: 270 · 2020: 214 · 2019: 191 · 2018: 195 · 2017: 183 · 2016: 196 · 2015: 180 · 2014: 183 · 2013: 157 · 2012: 137
- FWCI
- 90.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 928 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Natural Science Foundation of China (11079016, 30600112, 30871255, 30971485/C0706)
- Ministry of Education of the People's Republic of China
- National Key Research and Development Program of China (2011CB910600, 2011CB965300)
- Project 985
- Major State Basic Research Development Program of China (2009CB918401, 2009CB918600)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- 2-hydroxyglutarate, oncometabolites, alpha-ketoglutarate-dependent dioxygenase, IDH1 mutation, IDH2 mutation, histone demethylase, 5-hydroxymethylcytosine, competitive inhibition, glioma, acute myeloid leukemia, DNA methylation, histone methylation, active site
- MeSH terms
- Animals, Binding, Competitive, Cytosine, DNA-Binding Proteins, Glioma, Glutarates, Histones, Humans, Mixed Function Oxygenases, Isocitrate Dehydrogenase, Ketoglutaric Acids, Models, Molecular, Oxalates, Oxidoreductases, N-Demethylating, Procollagen-Proline Dioxygenase, Proto-Oncogene Proteins, Gene Expression, Caenorhabditis elegans, Homeodomain Proteins, Amino Acid Substitution, Catalytic Domain, Caenorhabditis elegans Proteins, Endostatins, 5-Methylcytosine, F-Box Proteins, Cell Line, Tumor, Dioxygenases, Hypoxia-Inducible Factor 1, alpha Subunit, Biocatalysis, Histone Demethylases, Jumonji Domain-Containing Histone Demethylases, Hypoxia-Inducible Factor-Proline Dioxygenases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
