Tumor metabolism and bioenergetics are important areas for cancer research and present promising targets for anticancer therapy. Growing tumors alter their metabolic profiles to meet the bioenergetic and biosynthetic demands of increased cell growth and proliferation. These alterations include the well-known aerobic glycolysis, the Warburg effect, which has been considered as the central tenet of cancer cell metabolism for more than 80 years [1]. Interest in cancer cell metabolism has been refueled by recent advances in the study of signaling pathways involving known oncogene and tumor suppressor genes, which reveal their close interaction with metabolic pathways [2-4]. For example, recent studies document an important role of glutamine catabolism in tumor stimulated by the oncogenic transcriptional factor c-MYC (herein termed MYC) which has been previously shown to stimulate glycolysis [5, 6]. Although glucose and glutamine serve as the main metabolic substrate for tumor cells, proline as a microenvironmental stress substrate has attracted lots of attention due to its unique metabolic system, its availability in tumor microenvironments and its responses to various stresses.