About this Research Topic
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 flow into NAD+/NADH, NADP+/NADPH and FAD/FADH2 redox couples, which represent the principal cofactors of dehydrogenases and reductases used by the cells to sustain all endergonic processes. In particular, NAD+/NADH and FAD/FADH2 are required to generate ATP that, in turn, provides the energy for all biochemical routines of the cell, such as biosynthetic and catabolic reactions; ion fluxes; cell motility; intracellular transport. NADP+/NADPH is indispensable to provide reducing equivalents needed to restore the antioxidant systems (e.g., the glutathione redox system), thus preventing reactive oxygen and nitrogen species (ROS and RNS)-induced oxidative stress and damage.
Studies of the last two decades have highlighted that cancer cells reprogram the metabolic circuitries that produce and utilize redox coenzymes 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 in which cells are exposed to relentless growth and proliferation stimuli. Among these, ROS, as well as nitric oxide (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. This is clearly shown by mutations that lead to the accumulation of oncometabolites, i.e. metabolites that can induce the tumorigenic process by changing the transcriptional and epigenetic landscape of tumor cells.
Metabolic changes and altered redox state that characterize cancer cells sustain their “individualistic” behavior under a teleonomic viewpoint. Indeed, malignant cells become able to overcome the adverse conditions they encounter in the process of neoplastic transformation, such as nutrient paucity, immune responses or anticancer therapies, thus profoundly subverting their homeostatic equilibrium with the rest of the organism. As a corollary, 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.
We welcome original research contributions, short communications, review articles and commentaries aimed at generating discussion and improving knowledge on the involvement, effects and intimate relationship of metabolic and redox-signaling pathways in each phase of tumorigenesis. We also foster to present articles dealing with new findings on redox regulation of metabolic enzymes and/or proteins that concur to adapt cellular bioenergetics to the metabolic needs of cancer. This Research Topic is also aimed at elaborating on the dual role played by mitochondria as redox and metabolic tuner of cancer cells, and, in turn, target of new anti-cancer therapies.
Keywords: Mitochondria and bioenergetics, tumor metabolism, oncometabolites, redox signaling, ROS and nitric oxide
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