13C Metabolic Flux Analysis of Metabolic Reprogramming Induced by AKT Signaling in Cancer Cells

摘要

At a molecular level, cancer is a disease of deregulated cell growth arising from genetic mutations that result in improper cell signaling. A key enzyme in mediating cellular growth response is the Akt serine/threonine kinase enzyme. This enzyme mediates a host of proliferative and survival responses including advancing cell cycle progression, increasing rate of biosynthesis, and increasing apoptotic resistance. Hyperactivation of the Akt signaling axis is implicated in a number of cancers including prostate, breast, lung, and colon cancers. Akt is also known to exhibit profound regulation of central carbon metabolism at the transcriptional, translational, post-translational, and allosteric levels. Prior biochemical studies of Akt have shown that its activation leads to increased expression of glycolytic enzymes including the GLUT1 glucose transporter and hexokinase (HK), two rate-limiting enzymes in glycolysis.