PGC1α Expression Defines a Subset of Human Melanoma Tumors with Increased Mitochondrial Capacity and Resistance to Oxidative Stress

By F. Vazquez, Ji‐Hong Lim, H. Chim, K. Bhalla, G. Girnun, K. Pierce, C. Clish, S. Granter, H. Widlund, B. Spiegelman and 1 more. Cancer Cell, 2013

624 citations recorded by the source corpus.

SUMMARY 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 ROS detoxification capacities that enables 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/18e17b0d2df766b8e571589c5dd0529d19e95113

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In Molecular Biology

1. T. Graeber
2. Larry Norton
3. Walter Kolch
4. Catherine S. Grasso
5. D. Lyden
6. C. Hill
7. Bernhard Schmierer

Citations in the corpus

• PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism (2020, background): “In fact, in different cancer cells, PGC-1α upregulation promotes cell survival by protecting cells from excessive mitochondrial ROS generation [81, 82].”
• Understanding the intersections between metabolism and cancer biology (2017, neutral): “Higher PGC1α expression portends poor outcome in human melanoma (Vazquez et al., 2013).”
• Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer (2017, positive): “While decreased mtDNA copy number reduces replication, conferring resistance to antineoplastic drugs such as anthracyclines and taxanes (41, 42), efficient mitochondria biogenesis would make cells more resistant to antimitochondrial agents, as was demonstrated in melanomas treated with BRAF inhibito”
• Multi-stage differentiation defines melanoma subtypes with differential vulnerability to drug-induced iron-dependent oxidative stress (2018, background): “MITF has also been shown to drive the expression of PGC1a, a key transcription factor regulating mitochondria biogenesis and expression of ROS detoxifying enzymes (Vazquez et al., 2013).”
• Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity (2020, background): “In contrast, melanoma cells with low expression of PGC1a favor glycolysis and are more susceptible to high ROS levels, indicating that these cells could potentially be targeted by ROS-inducing drugs [163].”