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Proteomic analysis of β‐catenin activation in mouse liver by DIGE analysis identifies glucose metabolism as a new target of the Wnt pathway
Author(s) -
Chafey Philippe,
Finzi Laetitia,
Boisgard Raphael,
Caüzac Michèle,
Clary Guillem,
Broussard Cédric,
Pégorier JeanPaul,
Guillonneau François,
Mayeux Patrick,
Camoin Luc,
Tavitian Bertrand,
Colnot Sabine,
Perret Christine
Publication year - 2009
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200800609
Subject(s) - wnt signaling pathway , proteomics , metabolism , catenin , microbiology and biotechnology , biochemistry , carbohydrate metabolism , biology , chemistry , computational biology , signal transduction , gene
The Wnt/β‐catenin signaling pathway has been increasingly implicated in liver development and physiology. Aberrant activation of this pathway is one of the major genetic events observed during the process of human HCC development. To gain insight into the mechanism underlying β‐catenin action in the liver, we conducted a quantitative differential proteomic analysis using 2‐D DIGE combined with MS, in mice with liver‐specific deletion of Apc resulting in acute activation of β‐catenin signaling (Apc KOliv mice). We identified 94 protein spots showing differential expression between mutant Apc KOliv and control mice, corresponding to 56 individual proteins. Most of the proteins identified were associated with metabolic pathways, such as ammonia and glucose metabolism. Our analysis showed an increase in lactate dehydrogenase activity together with a downregulation of two mitochondrial ATPase subunits (ATP5a1 and ATP5b). These observations indicate that β‐catenin signaling may induce a shift in the glucose metabolism from oxidative phosphorylation to glycolysis, known as the “Warburg effect”. Imaging with 18 F‐fluoro‐2‐deoxy‐ D ‐glucose‐positron emission tomography suggests that the specific metabolic reprogramming induced by β‐catenin in the liver does not imply the first step of glycolysis. This observation may explain why some HCCs are difficult to assess by fluoro‐2‐deoxy‐ D ‐glucose‐positron emission tomography imaging.