EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma

Hepatology. 2003 Jul;38(1):178-86. doi: 10.1053/jhep.2003.50270.


Wnt signaling mediated by beta-catenin plays crucial roles in the development of hepatocellular carcinoma and other cancers such as colorectal cancer. beta-Catenin associates with T-cell factor (TCF) transcription factors and functions as a transcriptional activator in the nucleus. By protein interaction screening, we identified EBP50, a cytoplasmic protein with 2 PDZ domains, as a beta-catenin-associating molecule. EBP50 interacted with beta-catenin through its carboxyl-PDZ domain in vitro and in vivo. Northern blot and RT-PCR analysis revealed an increase of EBP50 messenger RNA (mRNA) in hepatocellular carcinoma (HCC) cell lines and surgical specimens of human HCC. Over-expression of EBP50 protein with focal nuclear localization was detected in human HCC. In human HCC and colorectal cancer cell lines, EBP50 enhanced beta-catenin/TCF-dependent transcription in a dose-dependent manner. In an HCC cell line, over-expression of the carboxyl PDZ domain resulted in a decrease of endogenous beta-catenin/TCF transactivation. EBP50 promoted beta-catenin-mediated transactivation only in cells in which beta-catenin was already stabilized, suggesting that EBP50 may work with stabilized beta-catenin for transcriptional regulation. In conclusion, the EBP50/beta-catenin complex promotes Wnt signaling, and over-expression of EBP50 may work cooperatively with beta-catenin in the development of liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cloning, Molecular
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology
  • HeLa Cells
  • Humans
  • Liver Neoplasms*
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction / physiology
  • Sodium-Hydrogen Exchangers*
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Transcriptional Activation / physiology
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin


  • CTNNB1 protein, human
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Sodium-Hydrogen Exchangers
  • Trans-Activators
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • sodium-hydrogen exchanger regulatory factor