Regulation of β-catenin transcription activity by leupaxin in hepatocellular carcinoma

In human cancers, β-catenin is accumulated in the nucleus and activates mRNA transcription of many oncogenic genes, such as cyclin D1 and c-myc. However, the mechanism of β-catenin-mediated transcriptional activation remains largely unknown. In the present study, we identified leupaxin, an adaptor protein sharing homology with the focal adhesion protein, as a novel coactivator for β-catenin in human hepatocellular carcinoma (HCC). We show that leupaxin could interact with β-catenin and enhance its transcriptional activity through recruitment of coactivator complex, including steroid receptor coactivator 1 (SRC-1) and P300. As a result, leupaxin regulates HCC cell proliferation and cell-cycle progression in the presence of intact Wnt/β-catenin signaling. Furthermore, leupaxin is overexpressed in HCC tissues and correlated with mRNA levels of cyclin D1 and c-myc. Therefore, this is the first demonstration of a role for the leupaxin in the regulation of HCC progression, at least in part, by enhancing β-catenin transcription activity.