Proteomic analysis of β-catenin activation in mouse liver by DIGE analysis identifies glucose metabolism as a new target of the Wnt pathway

摘要: The Wnt/beta-catenin signaling pathway has been increasingly implicated in liver development and physiology. Aberrant activation of this is one the major genetic events observed during process human HCC development. To gain insight into mechanism underlying beta-catenin action liver, we conducted a quantitative differential proteomic analysis using 2-D DIGE combined with MS, mice liver-specific deletion Apc resulting acute (Apc(KOliv) mice). We identified 94 protein spots showing expression between mutant Apc(KOliv) control mice, corresponding to 56 individual proteins. Most proteins were associated metabolic pathways, such as ammonia glucose metabolism. Our showed an increase lactate dehydrogenase activity together downregulation two mitochondrial ATPase subunits (ATP5a1 ATP5b). These observations indicate that may induce shift metabolism from oxidative phosphorylation glycolysis, known "Warburg effect". Imaging (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography suggests specific reprogramming induced by does not imply first step glycolysis. This observation explain why some HCCs are difficult assess fluoro-2-deoxy-D-glucose-positron imaging.