WDR34 Activates Wnt/Beta-Catenin Signaling in Hepatocellular Carcinoma.

Abstract

Wnt ligand binding initiates the interaction between Frizzled and Dvl proteins. However, the regulation of Frizzled-Dvl proteins interaction remains largely unknown. The present study aims to elucidate the regulation of Frizzled-Dvl interaction by WDR34. The protein levels of WDR34 in hepatocellular carcinoma (HCC) tissues were examined by western blot and immunohistochemistry. The effects of WDR34 on the growth and migration of HCC cells were examined using MTT assay and Boyden chamber assay. The interaction between Frizzled and Dvl was evaluated by immunoprecipitation and GST pull-down assay. In this study, we have shown that WDR34, the binding protein of Frizzled (Fz) activated beta-catenin/TCF signaling by enhancing the interaction between Fz and Dvl2. WDR34 was found to up-regulate in HCC tissues, and its expression was negatively correlated with the survival of HCC patients. WDR34 promoted the growth, colony formation and migration of HCC cells. However, knocking down the expression of WDR34 inhibited the growth, colony formation and migration of HCC cells. Taken together, this study demonstrated the oncogenic roles of WDR34 in the progression of HCC and suggested that WDR34 might be a therapeutic target for HCC.