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.
(c) 2009 Wiley-Liss, Inc.