A Selective Inhibitor of Ubiquitin-Specific Protease 4 Suppresses Colorectal Cancer Progression by Regulating β-Catenin Signaling

• DOI: 10.33594/000000127
• Publication Date: 2019-06-28T06:30:44Z
• Authors: Hồng Hoa Nguyễn; Truc Kim; Thành Nguyễn; Myong-Joon Hahn; Sun-Il Yun; Kyeong Kyu Kim
• Keywords: Deubiquitinating enzyme

Dysregulation of deubiquitinating enzymes (DUBs), which regulate the stability key proteins, has been implicated in many human diseases, including cancers. Thus, DUBs can be considered as potential therapeutic targets for diseases. Among them, USP4 proposed a promising target colon cancer drugs since controls β-catenin, factor Wnt signaling involved tumorigenesis colorectal cancer. However, developing DUB inhibitors hindered because harbor similar active site structures and show broad substrate specificities.By performing vitro activity assays using chemical library, we identified several inhibitors. only neutral red (NR) showed selective inhibitory on cell-based assay system. In cells, NR affected protein shown by immunoblotting, it gene expression quantitative real-time PCR. NR's an anticancer drug was further estimated colony formation cell migration mouse xenograft model.We uncompetitive inhibitor validated its effects NR-treated cells decreased β-catenin reduced genes. Additionally, treating with significantly migration, injecting into model tumor volume.The current results suggest that could developed targeting USP4, they support possibility specific agents.