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WAVE3 promotes epithelial-mesenchymal transition of gastric cancer through upregulation of Snail.
Cancer Gene Therapy 2014 December
WAVE3, an actin cytoskeleton remodeling protein overexpressed in many kinds of cancers, has been associated with a lot of metastatic diseases. However, the role and mechanisms of the high expression of WAVE3 in human gastric cancer has not been fully elucidated. Here we demonstrated that WAVE3 was expressed in all six kinds of gastric-cancer cell lines: BGC-823, SGC-7901, AGS, MGC803, MKN28 and MKN45. Furthermore, a correlation was found between aggressiveness of these cell lines and expression of WAVE3. Next, we investigated the role of WAVE3 in SGC-7901 cells and found that upregulating WAVE3 could promote the migration, invasion and proliferation of SGC-7901 cells in vitro. It has been reported that WAVE3 could induce cancer invasion and metastasis by participating epithelial-mesenchymal transition (EMT). However, the mechanisms are not entirely clear. In this study we showed that elevated WAVE3 levels could induce EMT in SGC-7901 cells by dampening the expression of E-cadherin while increasing the expression of vimentin. Elevated WAVE3 levels could also improve the expression of transcription factor Snail. In addition, downregulating Snail could particularly reduce EMT and the metastasis, invasion and proliferation activity in SGC-7901 cells elevated by overexpression of WAVE3. Taken together, we demonstrated that WAVE3 promoted gastric-cancer-cells migration and invasion by taking part in EMT via upregulation of Snail. WAVE3 could be a useful target for gastric-cancer prevention and therapy.
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