Figure 1.

PGC-1α−mediated OxPhos activation and ROS generation promotes the metastatic cancer cell phenotype. Hypoxic non-metastatic cancer cells maintain a diminished level of mitochondrial metabolism. However, hypoxia causes PGC-1α (and HIF-1α, HIF-2α) overexpression which induces in pro-metastatic cells the generation of a higher number of mitochondria, increased OxPhos flux for ATP synthesis and increased ROS levels, all leading to the epithelial-mesenchymal transition and formation of highly metastatic cells. Abbreviations: OxPhos, oxidative phosphorylation; ROS, reactive oxygen species; HIF-1α, Hypoxia-Inducible Factor 1-alpha; PGC-1α, Peroxisome Proliferator-activated Receptor Gamma Co-activator 1-alpha.