Novel candidate targets of Wnt/β-catenin signaling in hepatoma cells

The activity of beta-catenin/TCF, the key component of Writ signaling pathway, is frequently deregulated in HCC, resulting in the activation of genes whose dysregulation has significant consequences on tumor development. Therefore, identifying the target genes of Writ signaling is important for understanding beta-catenin-mediated carcinogenesis. We analyzed the transcriptome profile of human hepatoma cell lines using cDNA microarrays representing 15,127 unique, liver-enriched gene loci to identify the target genes of p-catenin-mediated transcription (p < 0.005). This analysis yielded 130 potential Writ-associated classifier genes, and we found 33 of them contain consensus TCF-binding sites in presumptive transcriptional regulatory sequences. These genes were, then, tested for their Writ-dependence of expression in experimental models of Writ activation. Genes such as PPL29, NEDD4L, FUT8, LYZ, STMN2, STARD7 and KIAA0998 were proven to be up-regulated upon Wnt/beta-catenin activation. Gene ontology analysis of the 33 candidate genes indicated the presence of functional categories relevant to Writ pathway such as cell growth, proliferation, adhesion and signal transduction. In conclusion, we identified a number of candidate Wnt/beta-catenin target genes that can be useful for studying the role of altered Writ signaling in liver cancer development, and showed that some of them might be direct targets of Writ signaling in hepatoma cells. (c) 2006 Elsevier Inc. All rights reserved.