Proteomic analysis of beta-catenin activation in mouse liver by DIGE analysis identifies glucose metabolism as a new target of the Wnt pathway.
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.
Chafey
Philippe
P
Institut Cochin, Inserm U, Département Endocrinologie Métabolisme et Cancer, Université Paris Descartes, CNRS, France.
Finzi
Laetitia
L
Boisgard
Raphael
R
Caüzac
Michèle
M
Clary
Guillem
G
Broussard
Cédric
C
Pégorier
Jean-Paul
JP
Guillonneau
François
F
Mayeux
Patrick
P
Camoin
Luc
L
Tavitian
Bertrand
B
Colnot
Sabine
S
Perret
Christine
C
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*
D020543:Proteome; D051153:Wnt Proteins; D051176:beta Catenin; D005947:Glucose