The epigenetic basis of the Warburg effect.

Cancer development results from the accumulation of genetic and epigenetic changes. By interacting with intracellular signaling to promote carcinogenesis, epigenetic networks can actively transform cancer-promoting signals from tumor-permissive microenvironment to coordinate cellular proliferation and metabolism in the initiation and progression of cancers. As reported recently, NF-kappaB which can be activated by many soluble bioactive factors enriched in tumor microenvironments can promote the switch of cellular glucose metabolism from oxidative phosphorylation to oxygen-independent glycolysis in tumor cells, in addition to its well-known anti-apoptosis functions. Such epigenetic trans-generation of microenvironmental factors plays important roles in the development of cancers, particularly inflammation-related or sporadic cancers.