WDR34 Activates Wnt/Beta-Catenin Signaling in Hepatocellular Carcinoma

Dig Dis Sci. 2019 Sep;64(9):2591-2599. doi: 10.1007/s10620-019-05583-w. Epub 2019 Mar 15.

Abstract

Background: Wnt ligand binding initiates the interaction between Frizzled and Dvl proteins. However, the regulation of Frizzled-Dvl proteins interaction remains largely unknown.

Aims: The present study aims to elucidate the regulation of Frizzled-Dvl interaction by WDR34.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Beta-catenin/TCF signaling; Cell growth and migration; Hepatocellular carcinoma; WDR34.

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Dishevelled Proteins / metabolism*
  • Female
  • Frizzled Receptors / metabolism*
  • Gene Silencing
  • Humans
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Neoplastic Stem Cells
  • Survival Rate
  • Up-Regulation
  • Wnt Signaling Pathway*

Substances

  • Carrier Proteins
  • DVL2 protein, human
  • Dishevelled Proteins
  • Frizzled Receptors
  • WDR34 protein, human