The DOI matches its Crossref record; 52 of the 53 references it cites were found in a registry or an index.
IDH1 Mutation Induces Reprogramming of Pyruvate Metabolism
Open accessPublished version of a preprint
Abstract
Mutant isocitrate dehydrogenase 1 (IDH1) catalyzes the production of 2-hydroxyglutarate but also elicits additional metabolic changes. Levels of both glutamate and pyruvate dehydrogenase (PDH) activity have been shown to be affected in U87 glioblastoma cells or normal human astrocyte (NHA) cells expressing mutant IDH1, as compared with cells expressing wild-type IDH1. In this study, we show how these phenomena are linked through the effects of IDH1 mutation, which also reprograms pyruvate metabolism. Reduced PDH activity in U87 glioblastoma and NHA IDH1 mutant cells was associated with relative increases in PDH inhibitory phosphorylation, expression of pyruvate dehydrogenase kinase-3, and levels of hypoxia inducible factor-1α. PDH activity was monitored in these cells by hyperpolarized 13C-magnetic resonance spectroscopy (13C-MRS), which revealed a reduction in metabolism of hyperpolarized 2-13C-pyruvate to 5-13C-glutamate, relative to cells expressing wild-type IDH1. 13C-MRS also revealed a reduction in glucose flux to glutamate in IDH1 mutant cells. Notably, pharmacological activation of PDH by cell exposure to dichloroacetate (DCA) increased production of hyperpolarized 5-13C-glutamate in IDH1 mutant cells. Furthermore, DCA treatment also abrogated the clonogenic advantage conferred by IDH1 mutation. Using patient-derived mutant IDH1 neurosphere models, we showed that PDH activity was essential for cell proliferation. Taken together, our results established that the IDH1 mutation induces an MRS-detectable reprogramming of pyruvate metabolism, which is essential for cell proliferation and clonogenicity, with immediate therapeutic implications. Cancer Res; 75(15); 2999–3009. ©2015 AACR.
Overview
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
Verification
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?
In the citing paper
“one likely role is as an inflammatory signal, acting via SUCNR14,5,161,162.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [162]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
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
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784
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
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
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
Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR
Ardenkjær‐Larsen, J. H., Fridlund, B., Gram, A., Hansson, G., Hansson, L., Lerche, M. H., Servin, R., Thaning, M., & Golman, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1733835100 · Cited by 2,870
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
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
Research works printed but not linked: 1
- Warburg, 1924, Ueber den Stoffwechsel der Tumoren, Biochemische Zeitschrift, 152, 319
Cited by
Sorted by citations
Items 101–124 of 124
Innovating Metabolic Biomarkers for Hyperpolarized NMR
Hesketh, R. L., Wright, A. J., & Brindle, K. M. (2021) · Springer eBooks · doi:10.1007/978-3-030-55043-1_7 · Cited by 2
Cancer insights from magnetic resonance spectroscopy of cells and excised tumors
Penet, M., Sharma, R. K., Bharti, S. K., Mori, N., Artemov, D., & Bhujwalla, Z. M. (2022) · NMR in Biomedicine · doi:10.1002/nbm.4724 · Cited by 2
Carbohydrate Metabolism Parameters of Adult Glial Neoplasms According to Immunohistochemical Profile
Obukhova, L. M., Nikiforova, O., Kontorshchikova, C. N., Medyanik, I. A., Orlinskaya, N., Grishin, A., Kontorshchikov, М. М., & Щелчкова, Н. А. (2022) · Biomedicines · doi:10.3390/biomedicines10051007 · Cited by 2
Yang, Q., Hao, J., Zhang, H., Chi, M., Wang, Y., Li, Y., Huang, J., Wan, L., Xu, R., Zhao, X., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1246702/v1 · Cited by 2
Núñez, F. J., Banerjee, K., Mujeeb, A., Mauser, A., Tronrud, C. E., Zhu, Z., Raghuram, S., Sheth, M. R., Agudelo, J. A. P., Zelaya, J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.08.584091 · Cited by 2
Dong, H., Pham, J. M., Lauria, M. V., Atienza, C., Sloman, B., Barry, P., Davis, J., Saracen, M. J., Kishan, A. U., Raldow, A. C., et al. (2025) · Cancers · doi:10.3390/cancers17162708 · Cited by 1
Todeschi, J., Cébula, H., Bund, C., & Namer, I. J. (2025) · Metabolites · doi:10.3390/metabo16010017 · Cited by 1
Kundu, I. G., Toro, N., Mochizuki, A. Y., Langhnoja, J., Ayyagari, R. V., Cronk, J. C., Reel, S. M., Arounleut, P., Esqueda, L. T., Fuller, C. E., et al. (2026) · Neuro-Oncology · doi:10.1093/neuonc/noag228 · Cited by 1
Self-citationWu, S., Sheng, L., Fan, S., Guo, X., Zhu, B., Wu, C., & Lei, B. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1180662 · Cited by 1
Impact of San-mediated Signaling on Glioblastoma and Neuroblastoma Metabolism
Silva, M. R. (2018) · FIU - Digital Commons (Florida International University) · doi:10.25148/etd.fidc006885
Stuani, L., Sabatier, M., Millard, P., Palama, T., Poupin, N., Saland, E., Bosc, C., Tonini, L., Gales, L., Montersino, C., et al. (2018) · SSRN Electronic Journal · doi:10.2139/ssrn.3255557
The ketogenic diet is not effective in preclinical models of IDH1 wild-type and IDH1 mutant gliomaPreprint
Javier, R. A., & Horbinski, C. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.23.166652
Integration into cancer studies
Viswanath, P. (2021) · Advances in magnetic resonance technology and applications · doi:10.1016/b978-0-12-822269-0.00010-5
Self-citationPROSPECTS OF USING THE ELEMENTAL STATUS OF BLOOD TO ASSESS THE MOLECULAR GENETIC PROFILE OF GLIOMAS
Obukhova, L. M., Евдокимов, И. И., Medyanik, I. A., Orlinskaya, N. Y., Grishin, A., Babintsev, V. E., Barinov, Y. A., Kontorshchikov, М. М., Горшкова, Т. Н., & Lazukin, V. F. (2022) · Russian Clinical Laboratory Diagnostics · doi:10.51620/0869-2084-2022-67-9-497-503
Batsios, G., Taglang, C., Tran, M., Stevers, N. O., Barger, C. J., Gillespie, A. M., Ronen, S. M., Costello, J., & Viswanath, P. (2023) · doi:10.1158/1078-0432.22486158.v1
Self-citationBatsios, G., Taglang, C., Tran, M., Stevers, N. O., Barger, C. J., Gillespie, A. M., Ronen, S. M., Costello, J., & Viswanath, P. (2023) · doi:10.1158/1078-0432.22486158
Self-citationLee, G., Lee, S. M., Lee, S., Jeong, C. W., Song, H., Lee, S. Y., Yun, H., Koh, Y., & Kim, H. U. (2024) · Figshare · doi:10.6084/m9.figshare.25389925
Lee, G., Lee, S. M., Lee, S., Jeong, C. W., Song, H., Lee, S. Y., Yun, H., Koh, Y., & Kim, H. U. (2024) · Figshare · doi:10.6084/m9.figshare.25389463
Kume, S., Gomyo, M., Kobayashi, K., Saito, K., Shimizu, S., Suzuki, K., Maruyama, K., Tsuchiya, K., Shiokawa, Y., Tanaka, Y., et al. (2026) · Research Connections · doi:10.1093/rescon/vmag015
Li, Y. (2025) · Asilomar Conference on Signals, Systems and Computers (ACSSC) · doi:10.1109/ieeeconf67917.2025.11443753
Wu, R., Zhang, L., Wong, P. J. C., Sun, C., Feng, Y., Wang, X., Fu, M., Zhang, J., Qiu, F., Chen, X., et al. (2026) · Biomarker Research · doi:10.1186/s40364-026-00962-8
From metabolite mapping to precision imaging: advances in in vivo MR spectroscopy of brain tumours
Singh, M., Dwivedi, D. K., & Jagannathan, N. R. (2026) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2026.110784
Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma
Núñez, F. J., Banerjee, K., Mujeeb, A., Mauser, A., Tronrud, C. E., Zhu, Z., Raghuram, S., Sheth, M. R., Agudelo, J. A. P., Zelaya, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-77320-7 · Cited by 1
GLP1R agonists and vorasidenib converge on peroxynitrite-mediated cytotoxicity in mutant IDH gliomaPreprint
Taglang, C., Udutha, S., Phoenix, T. N., Lathia, J. D., de Groot, J., & Viswanath, P. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.18.759957
Self-citation
Metadata
- Authors
- Izquierdo-Garcia, J. L., Viswanath, P., Eriksson, P., Cai, L., Radoul, M., Chaumeil, M. M., Blough, M., Luchman, H. A., Weiss, S., Cairncross, J. G., Phillips, J. J., Pieper, R. O., & Ronen, S. M.
- Affiliations
- 1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California.
- University of California, San Francisco (US)
- University of Calgary (CA)
- Corresponding author
- Ronen, Sabrina M.
- ORCID
- Venue
- Cancer Research
- Published
- 2015-08-01
- Volume
- 75
- Issue
- 15
- Pages
- 2999-3009
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC4526330
- OpenAlex
- W2140821112
- Cited by
- 123
- References
- 53
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 6 · 2023: 10 · 2022: 11 · 2021: 13 · 2020: 18 · 2019: 12 · 2018: 15 · 2017: 14 · 2016: 8 · 2015: 3
- FWCI
- 4.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (R21CA161545, R01CA172845, R01CA154915)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Keywords
- IDH1 mutation, pyruvate metabolism, pyruvate dehydrogenase, 2-hydroxyglutarate, hypoxia-inducible factor-1α, dichloroacetate, hyperpolarized [1-13C]pyruvate, glutamate synthesis, glioblastoma, astrocytes, cell proliferation, clonogenicity, metabolic reprogramming
- MeSH terms
- Astrocytes, Dichloroacetic Acid, Glioblastoma, Glutarates, Humans, Isocitrate Dehydrogenase, Mutation, Magnetic Resonance Spectroscopy, Pyruvate Dehydrogenase Complex, Pyruvates, Down-Regulation, Glutamic Acid, Cell Line, Tumor, Cell Proliferation
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
