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.
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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)
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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
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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
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