Cell Stress, Metabolic Reprogramming and Cancer

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis. Mitochondria, beyond being the site of aerobic respiration, are at the crossroads of a variety of metabolic and signaling pathways resulting key regulatory organelles in cell life and death decision. Thus, it is no surprise that genomic, functional and structural mitochondrial alterations have been associated with cancer and that mitochondria have become a pharmacological target in cancer therapy. Proliferating tumor cells show increased glycolysis and convert the majority of glucose to L-lactate, even in normoxic conditions. This is known as the Warburg effect. Actually, in many tumors mitochondria are not defective in oxidative phosphorylation, and in the last decade, the molecular basis of Warburg effect has been reconsidered in the context of a set of concerted changes in energy metabolism and mitochondrial function that support tumorigenesis. This process, referred to as reprogramming of energy metabolism, is an emerging hallmark of cancer development. Metabolic reprogramming is driven by oncogenic changes of specific cell-signaling pathways and tumor microenvironment. Although much circumstantial clinical and experimental evidence exists of the peculiar metabolic features of cancer cells, the molecular mechanisms leading to cancer metabolic reprogramming, including the interplay between metabolism and epigenetics, are still elusive. This Research Topic is meant as a forum to present and discuss, in the form of research, mini-review or review articles, the achievements and perspectives in the research on the regulatory network and its key functional components which rewires cell metabolism in tumor transformation. The results of these studies are at the leading edge of cancer research and will lay the bases for the development of new therapies and the implementation of nutritional regimen for a healthy life as well as the improvement of anti-cancer therapies.