%0 Journal Article
%T YC-1 Antagonizes Wnt/¦Â-Catenin Signaling Through the EBP1 p42 Isoform in Hepatocellular Carcinoma
%A Ju-Yun Wu
%A Shih-Ping Lin
%A Tsai-Yuan Hsieh
%A Ya-Wen Lin
%A Yu-Lueng Shih
%J Archive of "Cancers".
%D 2019
%R 10.3390/cancers11050661
%X Novel drugs targeting Wnt signaling are gradually being developed for hepatocellular carcinoma (HCC) treatment. In this study, we used a Wnt-responsive Super-TOPflash (STF) luciferase reporter assay to screen a new compound targeting Wnt signaling. 3-(5¡ä-Hydroxymethyl-2¡ä-furyl)-1-benzylindazole (YC-1) was identified as a small molecule inhibitor of the Wnt/¦Â-catenin pathway. Our coimmunoprecipitation (co-IP) data showed that YC-1 did not affect the ¦Â-catenin/TCF interaction. Then, by mass spectrometry, we identified the ErbB3 receptor-binding protein 1 (EBP1) interaction with the ¦Â-catenin/TCF complex upon YC-1 treatment. EBP1 encodes two splice isoforms, p42 and p48. We further demonstrated that YC-1 enhances p42 isoform binding to the ¦Â-catenin/TCF complex and reduces the transcriptional activity of the complex. The suppression of colony formation by YC-1 was significantly reversed after knockdown of both isoforms (p48 and p42); however, the inhibition of colony formation was maintained when only EBP1 p48 was silenced. Taken together, these results suggest that YC-1 treatment results in a reduction in Wnt-regulated transcription through EBP1 p42 and leads to the inhibition of tumor cell proliferation. These data imply that YC-1 is a drug that antagonizes Wnt/¦Â-catenin signaling in HCC
%K hepatocellular carcinoma
%K YC-1
%K ¦Â-catenin/TCF
%K ErbB3 binding protein 1 (EBP1)
%K p42 isoform
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562864/