Premium
EBP50, a β‐catenin–associating protein, enhances Wnt signaling and is over‐expressed in hepatocellular carcinoma
Author(s) -
Shibata Tatsuhiro,
Chuma Makoto,
Kokubu Akiko,
Sakamoto Michiie,
Hirohashi Setsuo
Publication year - 2003
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2003.50270
Subject(s) - transactivation , pdz domain , wnt signaling pathway , beta catenin , cancer research , biology , catenin , transcription factor , gene knockdown , microbiology and biotechnology , cell culture , signal transduction , gene , genetics
Wnt signaling mediated by β‐catenin plays crucial roles in the development of hepatocellular carcinoma and other cancers such as colorectal cancer. β‐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 β‐catenin‐associating molecule. EBP50 interacted with β‐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 β‐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 β‐catenin/TCF transactivation. EBP50 promoted β‐catenin‐mediated transactivation only in cells in which β‐catenin was already stabilized, suggesting that EBP50 may work with stabilized β‐catenin for transcriptional regulation. In conclusion, the EBP50/β‐catenin complex promotes Wnt signaling, and over‐expression of EBP50 may work cooperatively with β‐catenin in the development of liver cancer.