Cited by 561Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer and biochemical research

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Pyruvate into lactate and back: From the Warburg effect to symbiotic energy fuel exchange in cancer cells

Feron, Olivier·2009·Radiotherapy and Oncology

DOI 10.1016/j.radonc.2009.06.025

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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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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)
DOI: 10.1016/j.radonc.2009.06.025
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Pyruvate into lactate and back: From the Warburg effect to symbiotic energy fuel exchange in cancer cells

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