Recently, Paras et al. [18] reported that Slug contributed to the down-regulation of E-cadherin expression in esophageal adenocarcinoma lines. Although both proteins are produced in all vertebrate species, their functions are VE-822 ic50 different among various species and different cells [32, 33]. These data suggest that E-cadherin production of carcinoma cells should be regulated by the different transcriptional repressors among the different cells or tissues. We found significant E-cadherin reduction in Slug overexpression cases, however, there were 28 (82.4%) with reduced E-cadherin

expression but without Slug overexpression. Kanai et al.[34] reported that 48% show DNA hypermethylation of the E-cadherin promoter region and 42% show loss of heterozygosity at the locus adjacent to the E-cadherin gene in HCC. Genetic mutation of the E-cadherin gene was detected Tideglusib in breast, gastric, and gynecological cancers, which showed a uniform loss of E-cadherin expression[35–37] . To date, a genetic mutation of the E-cadherin gene has not been reported in cases of EHC in which loss of E-cadherin expression is considered to be heterogeneous and reversible . Therefore, E-cadherin expression in EHC may be regulated not just by the Slug transcriptional factor but also by other genetic and/or epigenetic

alterations such as DNA mutation and/or methylation. Additional phosphatase inhibitor studies are required to reveal the entire regulatory mechanism of E-cadherin expression in EHC tumors. In this study, Slug mRNA overexpression correlated with metabasis and invasion of surgically resected human EHC. High expression of Slug mRNA has significantly shorter survival, the expression of Slug mRNA in EHC is an independent poor prognostic factor. EHC is hence a useful marker for predicting the outcome of patients with EHC who had a surgical resection of the tumor. Our data show that Slug, rather than Snail, negatively regulates E-cadherin expression, but it may also regulate the expression of other genes

involved in the invasive potential of EHC. E-Cadherin has been reported to involve in tumor invasiveness [38–42] , but the relationships between E-cadherin and mafosfamide clinicopathological factors were not consistent among these studies. In this study, E-cadherin was not found to be related to any clinicopathological factors. Differences of etiology and methods of evaluation might cause this discrepancy [40–42] . Additionally, the reversibility of E-cadherin expression should be considered. Slug and other family proteins bind to specific target genes and function as transcriptional repressors, but it is considered that the repression of E-cadherin alone is not sufficient to explain the role of Slug in cell migration and cancer development.