The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
Pyruvate into lactate and back: From the Warburg effect to symbiotic energy fuel exchange in cancer cells
Abstract
Tumor cells fuel their metabolism with glucose and glutamine to meet the bioenergetic and biosynthetic demands of proliferation. Hypoxia and oncogenic mutations drive glycolysis, with the pyruvate to lactate conversion being promoted by increased expression of lactate dehydrogenase A and inactivation of pyruvate dehydrogenase. The NAD+ pool is consecutively regenerated and supports the high glycolytic flux required to produce anabolic intermediates. Glutaminolysis provides metabolic intermediates such as alpha-ketoglutarate to feed and thereby maintain the tricarboxylic acid cycle as a biosynthetic hub. Glycolysis and glutaminolysis share the capacity to generate NADPH, from the pentose phosphate pathway and through the malate conversion into pyruvate, respectively. Both pathways ultimately lead to the secretion of lactate. More than a waste product, lactate was recently identified as a major energy fuel in tumors. Lactate produced by hypoxic tumor cells may indeed diffuse and be taken up by oxygenated tumor cells. Preferential utilization of lactate for oxidative metabolism spares glucose which may in turn reach hypoxic tumor cells. Monocarboxylate transporter 1 regulates the entry of lactate into oxidative tumor cells. Its inhibition favors the switch from lactate-fuelled respiration to glycolysis and consecutively kills hypoxic tumor cells from glucose starvation. Combination with radiotherapy renders remaining cells more sensitive to irradiation, emphasizing how interference with tumor cell metabolism may complement current anticancer modalities.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“Pyruvate is converted to acetyl-CoA through mitochondrial pyruvate dehydrogenase (PDH), whereas acetate is transported into cells and converted to acetyl-CoA through acetyl-CoA synthase (De Schrijver et al., 2003; Feron, 2009; Koukourakis et al., 2005; Pizer et al., 1996; Yoshimoto et al., 2001; Zaidi et al., 2012).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Feron, 2009
In the citing paper
“pyruvate or acetate can act as an alternative source to glucose and glutamine for lipid biosynthesis.”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Feron, 2009
Citations
Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
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
Kim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820
DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622
HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267
Gao, P., Tchernyshyov, I., Chang, T.-C., Lee, Y.-S., Kita, K., Ochi, T., Zeller, K. I., De Marzo, A. M., Van Eyk, J. E., Mendell, J. T., et al. (2009) · Nature · doi:10.1038/nature07823 · Cited by 2,124
Ras, PI(3)K and mTOR signalling controls tumour cell growth
Shaw, R. J., & Cantley, L. C. (2006) · Nature · doi:10.1038/nature04869 · Cited by 2,019
Cited by
Sorted by citations
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
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057
Danhier, F., Féron, O., & Véronique Préat, A. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.08.027 · Cited by 2,891
Glucose feeds the TCA cycle via circulating lactate
Hui, S., Ghergurovich, J. M., Morscher, R. J., Jang, C., Teng, X., Lu, W., Esparza, L. A., Reya, T., Zhan, L., Yanxiang Guo, J., et al. (2017) · Nature · doi:10.1038/nature24057 · Cited by 1,721
Interfering with pH regulation in tumours as a therapeutic strategy
Neri, D., & Supuran, C. T. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3554 · Cited by 1,551
Metadata
- Authors
- Feron, O.
- Venue
- Radiotherapy and Oncology
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 92
- Issue
- 3
- Pages
- 329-333
- ISSN
- 0167-8140 (ISSN-L)
- OpenAlex
- W2002922559
- Cited by
- 559
- References
- 38
- Citations by year
- 2026: 13 · 2025: 37 · 2024: 25 · 2023: 28 · 2022: 40 · 2021: 50 · 2020: 44 · 2019: 37 · 2018: 32 · 2017: 30 · 2016: 38 · 2015: 32 · 2014: 35 · 2013: 42 · 2012: 17
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Radiotherapy and Oncology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion)
- Funders
- Fonds De La Recherche Scientifique - FNRS
- 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
- Warburg effect, cancer metabolism, lactate, pyruvate, glycolysis, glutaminolysis, NAD+ regeneration, NADPH, pentose phosphate pathway, MCT1, LDHA, pyruvate dehydrogenase, hypoxia, oxidative metabolism, TCA cycle, alpha-ketoglutarate, glucose deprivation, combined radiotherapy
- MeSH terms
- Cell Survival, Energy Metabolism, Glycolysis, Humans, NAD, NADP, Neoplasms, Oxidation-Reduction, Radiation Tolerance, Sensitivity and Specificity, Cell Hypoxia, Cell Death, Pyruvic Acid, Lactic Acid, Cell Line, Tumor
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
