The DOI matches its Crossref record; 38 of the 41 references it cites were found in a registry or an index.
Acetate Is a Bioenergetic Substrate for Human Glioblastoma and Brain Metastases
Open accessAbstract
Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using (13)C-NMR analysis of brain tumors resected from patients during infusion of (13)C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-(13)C]acetate and can do so while simultaneously oxidizing [1,6-(13)C]glucose. The tumors do not oxidize [U-(13)C]glutamine. In vivo oxidation of [1,2-(13)C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together, the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth.
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
“The relevance of acetate as a potential fuel source has also been observed in vivo: in glioblastoma tumors resected from patients, up to half of the intramitochondrial acetyl-CoA pool is derived from circulating acetate (70).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [70]
In the citing paper
“Some cancer types, including liver and glioblastomas, readily take up acetate, which can be converted to acetyl-CoA by ACSS and undergo oxidation in the TCA cycle (70, 195).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [70]
In the citing paper
“Finally, extracellular acetate has recently been shown to be utilized by some cancers as a source of acetyl-CoA for biosynthesis.”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Mashimo et al., 2014
In the citing paper
“Specifically, a variety of tumor types localized to the brain, including primary glioblastomas as well as brain metastases that originated from other tissues, have been shown to assimilate exogenous acetate and incorporate acetate-derived carbons into de novo synthesized fatty acids (Comerford et al., 2014; Mashimo et al., 2014; Schug et al., 2015).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Mashimo et al., 2014
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
The Somatic Genomic Landscape of Glioblastoma
Brennan, C. W., Verhaak, R. G. W., McKenna, A., Campos, B., Noushmehr, H., Salama, S. R., Zheng, S., Chakravarty, D., Sanborn, J. Z., Berman, S. H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.034 · Cited by 5,016
The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism
Frost, G., Sleeth, M. L., Sahuri-Arisoylu, M., Lizarbe, B., Cerdan, S., Brody, L., Anastasovska, J., Ghourab, S., Hankir, M., Zhang, S., et al. (2014) · Nature Communications · doi:10.1038/ncomms4611 · Cited by 1,771
Serpins Promote Cancer Cell Survival and Vascular Co-Option in Brain Metastasis
Valiente, M., Obenauf, A. C., Jin, X., Chen, Q., Zhang, X. H.-F., Lee, D. J., Chaft, J. E., Kris, M. G., Huse, J. T., Brogi, E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.01.040 · Cited by 895
Comerford, S. A., Huang, Z., Du, X., Wang, Y., Cai, L., Witkiewicz, A. K., Walters, H., Tantawy, M. N., Fu, A., Manning, H. C., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.020 · Cited by 681 · cited 5×
“The current work and that of Comerford et al. (2014) underscores the value of in vivo studies in cancermetabolism.”
InfluentialSelf-citationEpidermal growth factor receptor and Ink4a/Arf
Bachoo, R. M., Maher, E. A., Ligon, K. L., Sharpless, N. E., Chan, S., You, M. J., Tang, Y., DeFrances, J., Stover, E. H., Weissleder, R., et al. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00046-6 · Cited by 659
Self-citationGlioblastoma: From Molecular Pathology to Targeted Treatment
Cloughesy, T. F., Cavenee, W. K., & Mischel, P. S. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130324 · Cited by 531
Marin-Valencia, I., Yang, C., Mashimo, T., Cho, S., Baek, H., Yang, X.-L., Rajagopalan, K. N., Maddie, M., Vemireddy, V., Zhao, Z., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.05.001 · Cited by 529
Self-citationImp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cellsPreprint
Janiszewska, M., Suvà, M. L., Riggi, N., Houtkooper, R. H., Auwerx, J. H., Clément‐Schatlo, V., Radovanovic, I., Rheinbay, E., Provero, P., & Stamenkovic, I. (2012) · Genes & Development · doi:10.1101/gad.188292.112 · Cited by 454
Ebert, D., Haller, R. G., & Walton, M. E. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-13-05928.2003 · Cited by 427
11C-acetate PET imaging in hepatocellular carcinoma and other liver masses.
Ho, C.-L., Yu, S. C. H., & Yeung, D. W. C. (2003) · PubMed · Cited by 380
Flagged first, then by citations
3 of the 41 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
Fundamentals of Cancer Metabolism
DeBerardinis, R. J., & Chandel, N. S. (2016) · Science Advances · doi:10.1126/sciadv.1600200 · Cited by 3,013
Self-citationMitochondrial 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
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119
The multifaceted roles of fatty acid synthesis in cancer
Röhrig, F., & Schulze, A. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.89 · Cited by 1,651
Metadata
- Authors
- Mashimo, T., Pichumani, K., Vemireddy, V., Hatanpaa, K. J., Singh, D. K., Sirasanagandla, S., Nannepaga, S., Piccirillo, S. G., Kovacs, Z., Foong, C., Huang, Z., Barnett, S., Mickey, B. E., DeBerardinis, R. J., Tu, B. P., Maher, E. A., & Bachoo, R. M.
- Affiliations
- Harold C. Simmons Comprehensive Cancer Center (US)
- The University of Texas Southwestern Medical Center (US)
- Children's Medical Center (US)
- Corresponding author
- Maher, Elizabeth A.
- Bachoo, Robert M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 159
- Issue
- 7
- Pages
- 1603-1614
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4374602
- OpenAlex
- W1992524428
- Cited by
- 760
- References
- 41
- Citations by year
- 2026: 32 · 2025: 69 · 2024: 64 · 2023: 64 · 2022: 88 · 2021: 77 · 2020: 66 · 2019: 64 · 2018: 53 · 2017: 69 · 2016: 71 · 2015: 41 · 2014: 2
- FWCI
- 19.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA154843, R01CA157996, P30CA142543)
- National Institute of Neurological Disorders and Stroke (R01NS065195)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015908, EB 015908)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Keywords
- acetate oxidation, glioblastoma, brain metastases, TCA cycle, acetyl-CoA, ACSS2, acetyl-CoA synthetase 2, glucose oxidation, cancer metabolism, 13C NMR, glutamine metabolism, tumor bioenergetics
- MeSH terms
- Acetates, Acetate-CoA Ligase, Animals, Brain Neoplasms, Citric Acid Cycle, Disease Models, Animal, Glioblastoma, Humans, Neoplasm Metastasis, Glutamic Acid, Mice
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
