13C-Pyruvate Imaging Reveals Alterations in Glycolysis that Precede c-Myc-Induced Tumor Formation and Regression
Open accessAbstract
Tumor cells have an altered metabolic phenotype characterized by increased glycolysis and diminished oxidative phosphorylation. Despite the suspected importance of glycolysis in tumorigenesis, the temporal relationship between oncogene signaling, in vivo tumor formation, and glycolytic pathway activity is poorly understood. Moreover, how glycolytic pathways are altered as tumors regress remains unknown. Here, we use a switchable model of Myc-driven liver cancer, along with hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) to visualize glycolysis in de novo tumor formation and regression. LDHA abundance and activity in tumors is tightly correlated to in vivo pyruvate conversion to lactate and is rapidly inhibited as tumors begin to regress, as are numerous glycolysis pathway genes. Conversion of pyruvate to alanine predominates in precancerous tissues prior to observable morphologic or histological changes. These results demonstrate that metabolic changes precede tumor formation and regression and are directly linked to the activity of a single oncogene.
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In early premalignant liver, MYC drives enhanced conversion of pyruvate to alanine, while later malignant lesions convert pyruvate to lactate.
“In early-stage, premalignant liver, MYC drives enhanced conversion of pyruvate to alanine, whereas later-stage malignant lesions convert pyruvate to lactate.”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [23]
Metabolic reprogramming precedes liver cancer in mice with MYC expression in hepatocytes.
“Metabolic reprogramming precedes liver cancer in mice with MYC expression in hepatocytes (23).”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [23]
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References 26 · Cited by 245
- Authors
- Hu, S., Balakrishnan, A., Bok, R. A., Anderton, B., Larson, P. E. Z., Nelson, S. J., Kurhanewicz, J., Vigneron, D. B., & Goga, A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Vigneron, Daniel B.
- Goga, Andrei
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 14
- Issue
- 1
- Pages
- 131-142
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3858338
- OpenAlex
- W1999565461
- Cited by
- 245
- References
- 26
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 10 · 2023: 11 · 2022: 14 · 2021: 20 · 2020: 17 · 2019: 15 · 2018: 15 · 2017: 22 · 2016: 12 · 2015: 22 · 2014: 19 · 2013: 23 · 2012: 19
- FWCI
- 7.29
- 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
- National Institutes of Health (5k08ca104032-05)
- University of California, San Francisco
- National Cancer Institute (R01CA136717, K08-CA104032, R21CA137298)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK026743)
- National Institute of Biomedical Imaging and Bioengineering (R01EB007588, P41EB013598)
- National Center for Research Resources (UL1RR024131)
- 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
- glycolysis, c-Myc, tumor regression, hyperpolarized [1-13C]pyruvate, magnetic resonance spectroscopic imaging, LDHA, pyruvate metabolism, alanine production, liver cancer, tumor metabolic reprogramming, oncogene signaling
- MeSH terms
- Alanine, Animals, Carbon Isotopes, Citric Acid Cycle, Disease Models, Animal, Glycolysis, L-Lactate Dehydrogenase, Liver Neoplasms, Magnetic Resonance Imaging, Mice, Transgenic, Signal Transduction, Proto-Oncogene Proteins c-myc, Pyruvic Acid, Gene Expression Profiling, Mice
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