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Antisense-Snail transfer inhibits tumor metastasis by inducing E-cadherin expression
Ali Zhang1, Gang Chen, Li Meng
1Cancer Biology Research Center, Tongji Hospital, Wuhan, Hubei 430040, China.
Abstract:
Carcinoma cell metastasis is mediated by increased mobility and invasiveness via epithelial-mesenchymal transition (EMT). Snail, a zinc-finger transcription factor, triggers EMT by directly repressing E-cadherin expression. In this study, the correlation between E-cadherin and Snail expression was investigated. In addition, the effect of antisense-Snail on the mobility and invasive properties of tumor cells in vitro and in vivo was assessed. Our data showed that Snail induced EMT, up-regulated mesenchymal gene expression and increased the ability of cancer cells to migrate and invade. In contrast, antisense-Snail prevented EMT by decreasing the expression of mesenchymal genes, and inhibited the migration and invasive potential in vitro. An in situ xenograft model showed that adenovirus-mediated antisense-Snail expression inhibited tumor cell metastasis to the lymph nodes and prolonged the survival of the hosts. These findings suggest that Snail plays a critical role in EMT and subsequent invasiveness. Snail inhibition may serve as a promising target for therapeutic strategies to prevent tumor metastasis.
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