Identification and in vivo analysis of putative Wnt target genes with effective roles in cancer

Abstract

One of the most common driving forces in hepatocellular carcinoma (HCC) is the aberrant activation of the Wnt/β-catenin signaling due to the accumulation of mutant β-catenin in the cell. Our group previously detected several genes with altered expression levels upon the overexpression of β-catenin in the HCC cell line, which are suggested to be novel Wnt/β-catenin targets that may play effective roles in cancer. In this study, our aim was to elucidate the roles of these putative Wnt/β-catenin target genes in tumorigenesis with an in vivo analysis in Drosophila. For this purpose, we downregulated the selected 16 putative Wnt/β-catenin target genes in two Drosophila cancer models using RNA interference (RNAi) and examined their effects on tumor and metastasis formations. Results from the RNAi screen revealed novel roles for the analyzed 16 putative Wnt/β-catenin target genes in tumorigenesis. The analyzed 13 putative Wnt/β-catenin target genes’ downregulations promoted tumor and metastasis formations in Drosophila, suggesting a tumor suppressor function; whereas the other 3 genes’ downregulations suppressed the tumor and metastasis formations and hindered the development in the analyzed tissues, suggesting an oncogenic or developmental role for these genes. These findings could serve to identify novel subjects for cancer research in order to provide insight into diagnostic and therapeutic processes of several cancer types as well as further characterization of the canonical Wnt/β-catenin signaling pathway.