Redox and Metabolic Circuits in CancerSalvatore Rizza, Andrea Rasola, Danyelle M. Townsend, Giuseppe Filomeni Frontiers Media SA, Dec 21, 2018 Living cells require a constant supply of energy for the orchestration of a variety of biological processes in fluctuating environmental conditions. In heterotrophic organisms, energy mainly derives from the oxidation of carbohydrates and lipids, whose chemical bonds breakdown allows electrons to generate ATP and to provide reducing equivalents needed to restore the antioxidant systems and prevent from damage induced by reactive oxygen and nitric oxide (NO)-derived species (ROS and RNS). Studies of the last two decades have highlighted that cancer cells reprogram the metabolic circuitries in order to sustain their high growth rate, invade other tissues, and escape death. Therefore, this broad metabolic reorganization is mandatory for neoplastic growth, allowing the generation of adequate amounts of ATP and metabolites, as well as the optimization of redox homeostasis in the changeable environmental conditions of the tumor mass. Among these, ROS, as well as NO and RNS, which are produced at high extent in the tumor microenvironment or intracellularly, have been demonstrated acting as positive modulators of cell growth and frequently associated with malignant phenotype. Metabolic changes are also emerging as primary drivers of neoplastic onset and growth, and alterations of mitochondrial metabolism and homeostasis are emerging as pivotal in driving tumorigenesis. Targeting the metabolic rewiring, as well as affecting the balance between production and scavenging of ROS and NO-derived species, which underpin cancer growth, opens the possibility of finding selective and effective anti-neoplastic approaches, and new compounds affecting metabolic and/or redox adaptation of cancer cells are emerging as promising chemotherapeutic tools. In this Research Topic we have elaborated on all these aspects and provided our contribution to this increasingly growing field of research with new results, opinions and general overviews about the extraordinary plasticity of cancer cells to change metabolism and redox homeostasis in order to overcome the adverse conditions and sustain their “individualistic” behavior under a teleonomic viewpoint. |
Contents
Redox and Metabolic Circuits in Cancer | 6 |
Metabolic Plasticity of Tumor Cell Mitochondria | 9 |
LonP1 Differently Modulates Mitochondrial Function and Bioenergetics of Primary Versus Metastatic Colon Cancer Cells | 30 |
Signaling Pathways Regulating Redox Balance in Cancer Metabolism | 43 |
The Role of Mitochondrial H+ATP Synthase in Cancer | 55 |
Phosphoinositide 3KinaseAkt Signaling and Redox Metabolism in Cancer | 63 |
Computational Structural Biology of Snitrosylation of Cancer Targets | 72 |
Role Targets and Regulation of denitrosylation in Malignancy | 95 |
Hypoxic Signalling in Tumour Stroma | 119 |
Activation of p62SQSTM1Keap1Nuclear Factor Erythroid 2Related Factor 2 Pathway in Cancer | 132 |
A Maestro With a Large Orchestra | 140 |
Involvement of NADPH Oxidase 1 in Liver Kinase B1Mediated Effects on Tumor Angiogenesis and Growth | 146 |
microRNA494 Favors HO1 Expression in Neuroblastoma Cells Exposed to Oxidative Stress in a Bach1Independent Way | 156 |
Novel MitochondriaTargeted Furocoumarin Derivatives as Possible AntiCancer Agents | 163 |
The Nutrient Game | 171 |
Back Cover | 182 |
The Mitochondrial Citrate Carrier SLC25A1 Sustains Redox Homeostasis and Mitochondrial Metabolism Supporting Radioresistance of Cancer Cells ... | 101 |