PGC1
Menée in vitro et in vivo, cette étude met en évidence le role joué par la surexpression de PGC1
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 PGC1
α (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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PGC1α is elevated in a subset of human melanoma tumors and derived cell lines
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PGC1α-positive melanoma cells exhibit increased mitochondrial metabolism
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PGC1α-positive melanoma cells exhibit increased ROS detoxification capacity
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PGC1α-negative melanoma cells are more glycolytic and sensitive to ROS-inducing drugs