PGC1α Expression Defines a Subset of Human Melanoma Tumors with Increased Mitochondrial Capacity and Resistance to Oxidative Stress
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Cancer cells reprogram their metabolism using different strategies to meet energy and anabolic demands to maintain growth and survival. Understanding the molecular and genetic determinants of these metabolic programs is critical to successfully exploit them for therapy. Here, we report that the oncogenic melanocyte lineage-specification transcription factor MITF drives PGC1α (PPARGC1A) overexpression in a subset of human melanomas and derived cell lines. Functionally, PGC1α positive melanoma cells exhibit increased mitochondrial energy metabolism and reactive oxygen species (ROS) detoxification capacities that enable survival under oxidative stress conditions. Conversely, PGC1α negative melanoma cells are more glycolytic and sensitive to ROS-inducing drugs. These results demonstrate that differences in PGC1α levels in melanoma tumors have a profound impact in their metabolism, biology, and drug sensitivity.
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Human melanoma has two distinct subgroups: a conventional glycolytic group and a group with high oxidative phosphorylation rates.
“recent studies have identified two distinct sub-groups in human melanoma: a conventional glycolytic group and a group characterised by high rates of oxidative phosphorylation 47,48 .”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [48]
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- Authors
- Vazquez, F., Lim, J.-H., Chim, H., Bhalla, K., Girnun, G., Pierce, K., Clish, C. B., Granter, S. R., Widlund, H. R., Spiegelman, B. M., & Puigserver, P.
- Affiliations
- Harvard University (US)
- University of Maryland, Baltimore (US)
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Puigserver, Pere
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 23
- Issue
- 3
- Pages
- 287-301
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3708305
- OpenAlex
- W2125408763
- Cited by
- 715
- References
- 49
- Citations by year
- 2026: 28 · 2025: 36 · 2024: 51 · 2023: 43 · 2022: 59 · 2021: 78 · 2020: 84 · 2019: 66 · 2018: 62 · 2017: 49 · 2016: 52 · 2015: 47 · 2014: 41 · 2013: 17 · 2012: 1
- FWCI
- 18.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA169919, P50CA093683)
- 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 › Melanoma and MAPK Pathways
- Keywords
- PGC-1α, melanoma, MITF, mitochondrial bioenergetics, oxidative stress resistance, reactive oxygen species scavenging, tumor metabolic reprogramming, glycolysis, drug sensitivity, transcriptional regulation
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Energy Metabolism, Heat-Shock Proteins, Humans, Melanocytes, Melanoma, Mitochondria, Oxygen Consumption, Transcription Factors, Apoptosis, Reactive Oxygen Species, Oxidative Stress, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Mice, Microphthalmia-Associated Transcription Factor, HEK293 Cells
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