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

Tatsuhiro Shibata, Makoto Chuma, Akiko Kokubu, Michiie Sakamoto, Setsuo Hirohashi

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalHepatology
Volume38
Issue number1
DOIs
Publication statusPublished - 2003 Jul 1
Externally publishedYes

Fingerprint

Catenins
Hepatocellular Carcinoma
PDZ Domains
TCF Transcription Factors
Liver Neoplasms
Cell Line
Transcriptional Activation
Colorectal Neoplasms
Proteins
Northern Blotting
Transcription Factors

ASJC Scopus subject areas

  • Hepatology

Cite this

EBP50, a β-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma. / Shibata, Tatsuhiro; Chuma, Makoto; Kokubu, Akiko; Sakamoto, Michiie; Hirohashi, Setsuo.

In: Hepatology, Vol. 38, No. 1, 01.07.2003, p. 178-186.

Research output: Contribution to journalArticle

Shibata, Tatsuhiro ; Chuma, Makoto ; Kokubu, Akiko ; Sakamoto, Michiie ; Hirohashi, Setsuo. / EBP50, a β-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma. In: Hepatology. 2003 ; Vol. 38, No. 1. pp. 178-186.
@article{654453228b444040b353481230961d51,
title = "EBP50, a β-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma",
abstract = "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.",
author = "Tatsuhiro Shibata and Makoto Chuma and Akiko Kokubu and Michiie Sakamoto and Setsuo Hirohashi",
year = "2003",
month = "7",
day = "1",
doi = "10.1053/jhep.2003.50270",
language = "English",
volume = "38",
pages = "178--186",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

TY - JOUR

T1 - EBP50, a β-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma

AU - Shibata, Tatsuhiro

AU - Chuma, Makoto

AU - Kokubu, Akiko

AU - Sakamoto, Michiie

AU - Hirohashi, Setsuo

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0038121958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038121958&partnerID=8YFLogxK

U2 - 10.1053/jhep.2003.50270

DO - 10.1053/jhep.2003.50270

M3 - Article

C2 - 12830000

AN - SCOPUS:0038121958

VL - 38

SP - 178

EP - 186

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 1

ER -