Twist1 causes the transcriptional repression of claudin-4 with prognostic significance in esophageal cancer.

Abstract

Twist1 is a transcription factor that is involved in epithelial-mesenchymal transition by suppressing intercellular adhesion. In this study, we aimed to determine the role of Twist1 in the regulation of claudin-4 expression and investigate its specific mechanisms and clinical implications using human esophageal carcinoma cell lines and tissues. As a result, up-regulation of Twist1 decreased both gene and protein expression levels of endogenous claudin-4 and the suppression was mediated by direct binding of Twist1 to the canonical E-box in the promoter region of claudin-4. In addition, there was a significant inverse correlation of claudin-4 with Twist1 in esophageal cancer tissues. High Twist1 and low claudin-4 expression was associated with the poorest prognosis and was more highly correlated with adverse outcome than any other subgroup with statistical significance (p=0.001). Our results indicate that Twist1 induces the repression of claudin-4 expression during the epithelial-mesenchymal transition in esophageal carcinoma.

• Authors: Keun-Woo Lee, Nam Kyung Lee, Jeong Hoon Kim, Myung Soo Kang, Hae Yong Yoo, Hyeon Ho Kim, Sung Hee Um, Seok-Hyung Kim
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 423 Issue 3 Pg. 454-60 (Jul 06 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 22668877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• CLDN4 protein, human
• Claudin-4
• Claudins
• Nuclear Proteins
• TWIST1 protein, human
• Twist-Related Protein 1

Topics

• Adolescent
• Adult
• Aged
• Base Sequence
• Carcinoma, Squamous Cell (genetics, mortality, pathology)
• Cell Line, Tumor
• Child
• Child, Preschool
• Claudin-4
• Claudins (antagonists & inhibitors, genetics)
• Disease-Free Survival
• Down-Regulation
• E-Box Elements
• Epithelial-Mesenchymal Transition (genetics)
• Esophageal Neoplasms (genetics, mortality, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Infant
• Infant, Newborn
• Middle Aged
• Molecular Sequence Data
• Nuclear Proteins (genetics, metabolism)
• Prognosis
• Promoter Regions, Genetic
• Twist-Related Protein 1 (genetics, metabolism)
• Young Adult