title: Proteomic analysis of beta-catenin activation in mouse liver by DIGE analysis identifies glucose metabolism as a new target of the Wnt pathway.
abstract: The Wnt/beta-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 beta-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 beta-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 beta-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 beta-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.
authors.affiliation: Institut Cochin, Inserm U, Département Endocrinologie Métabolisme et Cancer, Université Paris Descartes, CNRS, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chafey
authors.forename: Laetitia
authors.initials: L
authors.lastname: Finzi
authors.forename: Raphael
authors.initials: R
authors.lastname: Boisgard
authors.forename: Michèle
authors.initials: M
authors.lastname: Caüzac
authors.forename: Guillem
authors.initials: G
authors.lastname: Clary
authors.forename: Cédric
authors.initials: C
authors.lastname: Broussard
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pégorier
authors.forename: François
authors.initials: F
authors.lastname: Guillonneau
authors.forename: Patrick
authors.initials: P
authors.lastname: Mayeux
authors.forename: Luc
authors.initials: L
authors.lastname: Camoin
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
authors.forename: Sabine
authors.initials: S
authors.lastname: Colnot
authors.forename: Christine
authors.initials: C
authors.lastname: Perret
mesh_terms: D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017491:Genes, APC; D005947:Glucose / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D020543:Proteome / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D020543:Proteome; D051153:Wnt Proteins; D051176:beta Catenin; D005947:Glucose