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.