Proteomic analysis of β‐catenin activation in mouse liver by DIGE analysis identifies glucose metabolism as a new target of the Wnt pathway |
| |
Authors: | Philippe Chafey Laetitia Finzi Raphael Boisgard Michèle Caüzac Guillem Clary Cédric Broussard Jean‐Paul Pégorier François Guillonneau Patrick Mayeux Luc Camoin Bertrand Tavitian Sabine Colnot Christine Perret |
| |
Institution: | 1. Institut Cochin, Inserm U567, Département Endocrinologie Métabolisme et Cancer, Université Paris Descartes, CNRS, Paris, France;2. Institut Cochin, Inserm U567, Plate‐forme protéomique, Université Paris Descartes, CNRS, Paris, France;3. CEA, Institut d'Imagerie Biomedicale, Plateforme de Recherche en Imagerie Expérimentale, Inserm, Orsay, France;4. Institut Cochin, Inserm U567, Département d'Hématologie, Université Paris Descartes, CNRS, Paris, France |
| |
Abstract: | 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 (ApcKOliv mice). We identified 94 protein spots showing differential expression between mutant ApcKOliv 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 18F‐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. |
| |
Keywords: | Adenomatous polyposis coli β ‐catenin DIGE Mouse liver |
|
|