Dermatopontin inhibits WNT signaling pathway via CXXC finger protein 4 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major cause of tumor associated deaths globally. Annually, the prevalence of HCC is increasing and the lack of early prognostic indicators manifests a dismal prognosis for HCC patients. A deep understanding of the molecular events that promote HCC progression are required for the design of new diagnostics and therapeutics. Dermatopontin (DPT) is an extracellular matrix protein that regulates the metastatic phenotypes of many cancers. However, the effects of DPT on HCC cell growth remain undefined. In this study, we demonstrate that the exogenous expression of DPT inhibits HCC cell growth both in vitro and in vivo. Furthermore, we show that DPT regulates CXXC4, which in turn targets c-Myc, EZH2, SOX2 and β-catenin, through its ability to impact Wnt signaling pathway. These data suggest that DPT regulates CXXC4, c-Myc, EZH2, SOX2 and β-catenin, through Wnt signaling to repress HCC proliferation. This highlights DPT as promising target for future HCC diagnostics and therapeutic targets.