Twist1 causes the transcriptional repression of claudin-4 with prognostic significance in esophageal cancer.
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.
Department of Pathology, Sungkyunkwan University School of Medicine, South Korea.
Keun-Woo
KW
Lee
Nam Kyung
NK
Lee
Jeong Hoon
JH
Kim
Myung Soo
MS
Kang
Hae Yong
HY
Yoo
Hyeon Ho
HH
Kim
Sung Hee
SH
Um
Seok-Hyung
SH
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D062506:Claudin-4; D057167:Claudins / Q000037:antagonists & inhibitors / Q000235:genetics*; D018572:Disease-Free Survival; D015536:Down-Regulation; D024721:E-Box Elements; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
C568157:CLDN4 protein, human; D062506:Claudin-4; D057167:Claudins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1