Organ patterning in the adult stage: the role of Wnt/beta-catenin signaling in liver zonation and beyond.
Wnt/beta-catenin signaling has been found to play key roles in metabolic zonation of adult liver, regeneration, and hepatocellular carcinogenesis. In this review, recent progress in this field is summarized, in particular the rapidly growing knowledge about the various interactions of beta-catenin with many transcription factors involved in controlling metabolism. These interactions may provide the basis for understanding how the wide range of activities of Wnt/beta-catenin signaling is differentially interpreted. Based on these results, a three-level mode for the molecular interpretation of beta-catenin activity gradients in liver is proposed favoring cell differentiation, metabolic zonation, and proliferation. While derangement of the combinatorial interplay of the various transcription factors with beta-catenin at the intermediary activity level may contribute to the development of metabolic diseases, extremely high activation of beta-catenin may eventually lead to initiation and progression of hepatocellular tumors.
Gebhardt
Rolf
R
Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany. rgebhardt@medizin.uni-leipzig.de
Hovhannisyan
Amalya
A
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological; D020239:Receptor Cross-Talk / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin