Antisense-Snail transfer inhibits tumor metastasis by inducing E-cadherin expression.
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.
Zhang
Ali
A
Cancer Biology Research Center, Tongji Hospital, Wuhan, Hubei 430040, China.
Chen
Gang
G
Meng
Li
L
Wang
Quansheng
Q
Hu
Wei
W
Xi
Ling
L
Gao
Qinlei
Q
Wang
Shixuan
S
Zhou
Jiangfeng
J
Xu
Gang
G
Meng
Li
L
Ma
Ding
D
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008207:Lymphatic Metastasis / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors