S100A4 regulates motility and invasiveness of human esophageal squamous cell carcinoma through modulating the AKT/Slug signal pathway.

The involvement of S100A4 in modulating invasiveness of esophageal squamous cell carcinoma (ESCC) cell lines was explored. It was shown that S100A4 expression is positively correlated with the degree of invasiveness in human ESCC cells. The S100A4-rich EC-1 cells displayed higher migratory and invasive cell behavior while ET-1 cells with low S100A4 expression levels displayed lower migratory and invasive cell behavior. S100A4 silencing by small interfering (siRNA) in EC-1 cells induced E-cadherin expression, and overexpression of S100A4 in a lowly invasive TE-1 cells suppressed E-cadherin expression. It is suggested that S100A4 silencing inhibit invasion via E-cadherin upregulation, and overexpression of S100A4 promote invasion via E-cadherin downregulation in ESCC cells. Compared with the vector-transfected cells, S100A4 silencing in EC-1 cells showed reduced ability of migration and invasiveness, and overexpression of S100A4 in TE-1 cells showed increased ability of migration and invasiveness via wound-healing and Transwell assay, and pseudometastatic model assay. Furthermore, re-expression of S100A4 could increase the invasive phenotypes in S100A4 siRNA transfected EC-1 cells, and S100A4 silencing could decrease the invasive phenotypes in S100A4 circular DNA (cDNA) transfected TE-1 cells. It was found that Slug is downregulated in S100A4 siRNA transfected EC-1 cells, and Slug is upregulated in S100A4 cDNA transfected TE-1 cells. It was also discovered S100A4 cDNA induced protein kinase B (AKT) phosphorylation at Serine-473(phospho-AKT [p-AKT]) levels, followed by the Slug upregulation, and S100A4 siRNA decreases the phospho-AKT levels, followed by the Slug downregulation. The data suggested that S100A4 could regulate migratory and invasive behavior of human ESCC cells through modulating AKT/Slug pathway.

Zhang K ，Zhang M ，Zhao H ，Yan B ，Zhang D ，Liang J ... -  《-》

[Role of S100A4 in the epithelial-mesenchymal transition of esophageal squamous cell carcinoma and its molecular mechanism].

Jian L ，Zhihong W ，Liuxing W ，Qingxia F ... -  《-》

Slug down-regulation by RNA interference inhibits invasion growth in human esophageal squamous cell carcinoma.

Tang P ，Yu Z ，Zhang K ，Wang Y ，Ma Z ，Zhang S ，Chen D ，Zhou Y ... -  《BMC GASTROENTEROLOGY》

S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells.

Chen D ，Zheng XF ，Yang ZY ，Liu DX ，Zhang GY ，Jiao XL ，Zhao H ... -  《-》

Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism.

Zhang HF ，Alshareef A ，Wu C ，Li S ，Jiao JW ，Cao HH ，Lai R ，Xu LY ，Li EM ... -  《Oncotarget》