Abstract
BackgroundEpithelial–mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer.MethodsWe examined the effects of silenced or overexpressed Snail using lenti-viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue microarrays from 314 patients with gastric adenocarcinoma (GC) was used to determine Snail’s clinicopathological and prognostic significance. Differential gene expression in 45 GC specimens with Snail overexpression was investigated using cDNA microarray analysis.ResultsSilencing of Snail by shRNA decreased invasion and migration in GC cell lines. Conversely, Snail overexpression increased invasion and migration of gastric cancer cells, in line with increased VEGF and MMP11. Snail overexpression (≥75% positive nuclear staining) was also significantly associated with tumor progression (P < 0.001), lymph node metastases (P = 0.002), lymphovascular invasion (P = 0.002), and perineural invasion (P = 0.002) in the 314 GC patients, and with shorter survival (P = 0.023). cDNA microarray analysis revealed 213 differentially expressed genes in GC tissues with Snail overexpression, including genes related to metastasis and invasion.ConclusionSnail significantly affects invasiveness/migratory ability of GCs, and may also be used as a predictive biomarker for prognosis or aggressiveness of GCs.
Highlights
Epithelial–mesenchymal transition (EMT) plays a significant role in tumor progression and invasion
We evaluated Snail’s effect on invasiveness/migratory ability in gastric cancer cell lines, and investigated the possibility of Snail being used as a predictive marker for evaluating poor prognosis or tumor aggressiveness in gastric adenocarcinoma (GC) patients
In this study, we showed that Snail overexpression induced increased migration and invasion in gastric cancer cell lines
Summary
Epithelial–mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. This study investigated the role of Snail in gastric cancer. Epithelial–mesenchymal transition (EMT), a developmental process whereby epithelial cells reduce intercellular adhesion and acquire myofibroblastic features, is critical to tumor progression [1,2,3]. During EMT, significant changes occur, including downregulation of epithelial markers such as E-cadherin, translocation of β-catenin We evaluated Snail’s effect on invasiveness/migratory ability in gastric cancer cell lines, and investigated the possibility of Snail being used as a predictive marker for evaluating poor prognosis or tumor aggressiveness in GC patients. We evaluated the gene expression pattern in 45 GC tissues with Snail overexpression, using cDNA microarrays
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