Isotope tracing of human clear cell renal cell carcinomas demonstrates suppressed glucose oxidation in vivo
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Clear cell renal cell carcinoma (ccRCC) is the most common form of human kidney cancer. Histological and molecular analyses suggest that ccRCCs have significantly altered metabolism. Recent human studies of lung cancer and intracranial malignancies demonstrated an unexpected preservation of carbohydrate oxidation in the tricarboxylic acid (TCA) cycle. To test the capacity of ccRCC to oxidize substrates in the TCA cycle, we infused 13 C-labeled fuels in ccRCC patients and compared labeling patterns in tumors and adjacent kidney. After infusion with [U-13 C]glucose, ccRCCs displayed enhanced glycolytic intermediate labeling, suppressed pyruvate dehydrogenase flow, and reduced TCA cycle labeling, consistent with the Warburg effect. Comparing 13 C labeling among ccRCC, brain, and lung tumors revealed striking differences. Primary ccRCC tumors demonstrated the highest enrichment in glycolytic intermediates and lowest enrichment in TCA cycle intermediates. Among human tumors analyzed by intraoperative 13 C infusions, ccRCC is the first to demonstrate a convincing shift toward glycolytic metabolism.
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Clear cell renal carcinomas do not oxidize glucose-derived carbon in the TCA cycle and instead preferentially engage in aerobic glycolysis.
“Clear cell renal carcinomas exhibit a tumor type–specific metabolic profile: these tumors do not oxidize glucose-derived carbon in the TCA cycle and instead preferentially engage in aerobic glycolysis (197).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [197]
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- Authors
- Courtney, K. D., Bezwada, D., Mashimo, T., Pichumani, K., Vemireddy, V., Funk, A. M., Wimberly, J., McNeil, S. S., Kapur, P., Lotan, Y., Margulis, V., Cadeddu, J. A., Pedrosa, I., DeBerardinis, R. J., Malloy, C. R., Bachoo, R. M., & Maher, E. A.
- Affiliations
- Harold C. Simmons Comprehensive Cancer Center (US)
- Children's Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- VA North Texas Health Care System (US)
- Corresponding author
- Courtney, Kevin D.
- Maher, Elizabeth A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 28
- Issue
- 5
- Pages
- 793-800.e2
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC6221993
- OpenAlex
- W2888708599
- Cited by
- 280
- References
- 34
- Citations by year
- 2026: 26 · 2025: 28 · 2024: 31 · 2023: 49 · 2022: 31 · 2021: 43 · 2020: 35 · 2019: 33 · 2018: 4
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- ACS (IRG-02-196)
- NCI (P50CA196516, R01CA154475, R35CA220449)
- NIH (P41EB015908, KL2TR001103, R01CA154475, TL1TR001104)
- CPRIT (RP160089)
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- clear cell renal cell carcinoma, cancer metabolism, Warburg effect, glucose oxidation, TCA cycle, pyruvate dehydrogenase, glycolysis, 13C isotope tracing, tumor glucose metabolism
- MeSH terms
- Adult, Aged, Carbon Isotopes, Carcinoma, Renal Cell, Citric Acid Cycle, Glucose, Glycolysis, Humans, Kidney, Kidney Neoplasms, Middle Aged, Oxidation-Reduction
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