Negative Regulation of the Tight Junction Protein Tricellulin by Snail-Induced Epithelial-Mesenchymal Transition in Gastric Carcinoma Cells

<i>Objective:</i> Tricellulin plays a central role in the sealing of epithelia at tricellular contacts. We examined the effects of Snail, an epithelial-mesenchymal transition (EMT)-related transcription factor, on the regulation of tricellulin expression in human gastric carcinoma (GC)-derived cells. <i>Method:</i> Six human GC-derived cell lines were used in this study. Expression and localization of tricellulin was analyzed by reverse transcription (RT)-PCR and immunohistochemistry. Also, a <i>Snail</i> expression vector was transfected into HSC-45 cells to examine altered mRNA levels of <i>tricellulin,</i><i>E-cadherin</i>, <i>vimentin</i>, <i>N-cadherin </i>and several EMT transcription factors by quantitative real-time RT-PCR. <i>Results:</i> Abundant <i>tricellulin</i> expression was detected in all GC-derived cells examined. In HSC-45 cells, transduction of Snail decreased the expression levels of <i>tricellulin</i> and <i>E-cadherin</i> but increased <i>vimentin</i> and <i>N-cadherin,</i> which was accompanied by induction of EMT transcription factors such as <i>Twist1</i>, <i>Twist2</i> and <i>Slug</i>. In normal gastric mucosa, tricellulin protein was localized at the tricellular tight junction; however, in HSC-45 cells, tricellulin protein was distributed in the cytoplasm. In GC tissues, tricellulin expression at the cellular membrane was retained in a subset of EMT-negative GCs, and it disappeared in EMT-positive GCs. <i>Conclusions:</i> The findings in the present study suggest that repression of tricellulin expression may be related to Snail-induced EMT in human GCs.