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.
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“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
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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
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