Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance

Fantin, Valeria R.; St-Pierre, Julie; Leder, Philip

doi:10.1016/j.ccr.2006.04.023

Cited by 1,635Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer and biochemical research

Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance

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Fantin, Valeria R., St-Pierre, Julie, Leder, Philip·2006·Cancer Cell

DOI 10.1016/j.ccr.2006.04.023

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Abstract

Alterations in cellular metabolism are among the most consistent hallmarks of cancer. Herein we have investigated the relationship between increased aerobic lactate production and mitochondrial physiology in tumor cells. To diminish the ability of malignant cells to metabolize pyruvate to lactate, lactate dehydrogenase A (LDH-A) levels were knocked down by means of LDH-A short hairpin RNAs. Reduction in LDH-A activity resulted in stimulation of mitochondrial respiration and decrease of mitochondrial membrane potential. It also compromised the ability of these tumor cells to proliferate under hypoxia. The tumorigenicity of the LDH-A-deficient cells was severely diminished, and this phenotype was reversed by complementation with the human ortholog LDH-A protein. These results demonstrate that LDH-A plays a key role in tumor maintenance.

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From Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation (2016) · cites this paper as Fantin et al., 2006

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Authors: Fantin, V. R., St-Pierre, J., & Leder, P.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Leder, Philip
ORCID: Fantin, Valeria R.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2006-06
Volume: 9
Issue: 6
Pages: 425-434
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2006.04.023
OpenAlex: W2163471981
Cited by: 1,635
References: 45
Citations by year: 2026: 61 · 2025: 76 · 2024: 75 · 2023: 81 · 2022: 94 · 2021: 91 · 2020: 100 · 2019: 94 · 2018: 90 · 2017: 82 · 2016: 77 · 2015: 106 · 2014: 92 · 2013: 98 · 2012: 83
FWCI: 22.86
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2639 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
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: LDHA, aerobic glycolysis, mitochondrial respiration, mitochondrial membrane potential, tumor maintenance, hypoxia, tumor cell proliferation, tumorigenicity, cancer metabolism, pyruvate to lactate conversion
MeSH terms: Lactate Dehydrogenase 5, Adenosine Triphosphate, Animals, Cell Transformation, Neoplastic, Female, Glucose, Glycolysis, Humans, Indoles, Isoenzymes, L-Lactate Dehydrogenase, Mammary Glands, Animal, Mammary Neoplasms, Experimental, Membrane Potentials, Mitochondria, Neoplasm Transplantation, Oxidative Phosphorylation, Oxygen Consumption, Pyridinium Compounds, Cell Hypoxia, Lactic Acid, Cell Line, Tumor, Cell Proliferation, Mitochondrial Membranes, Mice

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Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance

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