title: Mitochondrial redox signaling and cancer invasiveness.
abstract: The concept that invasive cancer is associated with increased levels of reactive oxygen species (ROS) generated by mitochondria is consistent with an ROS-mediated signaling mechanism. As a tumor grows, it encounters adverse microenvironments, one of which is low oxygen (hypoxia), which selects tumor cells with characteristics of increased invasiveness. Hypoxic environments select for tumor cells with stabilized HIF1 apha, a transcription factor that regulates genes coding for pro-tumor cytokines that signal stromal cells such as macrophages and fibroblasts to support an invasive tumor cell phenotype. HIF1 alpha-mediated switches in the energy production of tumor cells from OXPHOS to glycolysis, as well as age-associated decreases in the metabolic rate of the host, enhance invasive qualities of tumor cells. An increase in environmental oxygen in combination with a mitochondrial targeted catalase mimetic and a metabolism booster may be of interest to investigate as a treatment strategy for invasive cancer.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Enns
authors.forename: Warren
authors.initials: W
authors.lastname: Ladiges
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D016207:Cytokines / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D015398:Signal Transduction
chemical_list: D016207:Cytokines; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins