Claudin 1 mediates TNFα-induced gene expression and cell migration in human gastric cancer cells.

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TNFα has been known to be produced in cancer cells as an endogenous tumor promoter, and involved in epithelial-mesenchymal transition. However, Claudin-1 is well known as one of tight junction proteins, recent studies also showed that the expression of Claudin-1 increased during tumor progression in cancer cells. In this study, we investigated the association between TNFα and Claudin-1 during tumor progression in human gastric cancer cells. Claudin-1 was significantly increased upon TNFα treatment in gastric cancer cells, and down-regulation of Claudin-1 using siRNA inhibited 70% of TNFα-induced gene expression and 87% of microRNA expression. Further, knocking-down of Claudin-1 decreased cell proliferation, migration and invasion, and increased apoptosis. Pathway analysis showed that cellular movement, including MMP7, TGFBR1 and TNFSF10, was the top-ranked signal network. In conclusion, Claudin-1 behaves as a crucial signal mediator in TNFα-induced gene expression and cell migration in gastric cancer cells.