BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1
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Here we show that glioblastoma express high levels of branched-chain amino acid transaminase 1 (BCAT1), the enzyme that initiates the catabolism of branched-chain amino acids (BCAAs). Expression of BCAT1 was exclusive to tumors carrying wild-type isocitrate dehydrogenase 1 (IDH1) and IDH2 genes and was highly correlated with methylation patterns in the BCAT1 promoter region. BCAT1 expression was dependent on the concentration of α-ketoglutarate substrate in glioma cell lines and could be suppressed by ectopic overexpression of mutant IDH1 in immortalized human astrocytes, providing a link between IDH1 function and BCAT1 expression. Suppression of BCAT1 in glioma cell lines blocked the excretion of glutamate and led to reduced proliferation and invasiveness in vitro, as well as significant decreases in tumor growth in a glioblastoma xenograft model. These findings suggest a central role for BCAT1 in glioma pathogenesis, making BCAT1 and BCAA metabolism attractive targets for the development of targeted therapeutic approaches to treat patients with glioblastoma.
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Tumors of other lineages, including some glioblastomas and blast crisis chronic myeloid leukemia, are also dependent on BCAA transaminases.
“Tumors of other lineages are also dependent on BCAA transaminases, including some glioblastomas and blast crisis chronic myeloid leukemia (Hattori et al., 2017; Tonjes et al., 2013).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Tonjes et al., 2013
Late-passage IDH1 mutant NHA cells had low BCAT1 protein levels.
“our late-passage IDH1 mutant NHA cells also had low BCAT1 protein levels.”
From Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma (2018) · cites this paper as Tonjes et al., 2013
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- Authors
- 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., Felsberg, J., Addington, A., Lemke, D., Weibrecht, I., Hovestadt, V., Rolli, C. G., Campos, B., Turcan, S., Sturm, D., Witt, H., Chan, T. A., Herold-Mende, C., Kemkemer, R., König, R., Schmidt, K., Hull, W.-E., Pfister, S. M., Jugold, M., Hutson, S. M., Plass, C., Okun, J. G., Reifenberger, G., Lichter, P., & Radlwimmer, B.
- Affiliations
- German Cancer Research Center (DE)
- Ewha Womans University (KR)
- Heinrich Heine University Düsseldorf (DE)
- Virginia Tech (US)
- Max Planck Institute for Intelligent Systems (DE)
- Heidelberg University (DE)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Radlwimmer, Bernhard
- ORCID
- Venue
- Nature Medicine
- Published
- 2013-06-23
- Volume
- 19
- Issue
- 7
- Pages
- 901-908
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4916649
- OpenAlex
- W2074983857
- Cited by
- 486
- References
- 71
- Citations by year
- 2026: 28 · 2025: 35 · 2024: 39 · 2023: 40 · 2022: 49 · 2021: 58 · 2020: 52 · 2019: 31 · 2018: 38 · 2017: 38 · 2016: 29 · 2015: 24 · 2014: 19 · 2013: 5
- FWCI
- 12.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Cancer Institute (T32CA160001)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- BCAT1, branched-chain amino acid catabolism, glioblastoma, IDH2, promoter methylation, alpha-ketoglutarate, tumor cell proliferation, tumor invasion, targeted therapy
- MeSH terms
- Amino Acids, Branched-Chain, Transaminases, Animals, Brain Neoplasms, Female, Glioma, Humans, Isocitrate Dehydrogenase, Metabolism, Mice, Nude, Models, Biological, Cell Line, Tumor, Cell Proliferation, Mice, HEK293 Cells
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 ›
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