Ghrelin promotes renal cell carcinoma metastasis via Snail activation and is associated with poor prognosis.

Ghrelin is an appetite-regulating molecule that promotes growth hormone (GH) release and food intake through growth hormone secretagogue receptor (GHS-R). Recently, high ghrelin levels have been detected in various types of human cancer. Ghrelin expression is observed in proximal and distal renal tubules, where renal cell carcinoma (RCC) arises. However, whether ghrelin is up-regulated and promotes renal cell carcinogenesis remains obscure. In this study, we observed that ghrelin was highly expressed in renal tumours, especially in metastatic RCC. In addition, high ghrelin levels correlated with poor outcome, lymph node and distant metastasis. The addition of ghrelin promoted the migration ability of RCC cell lines 786-0, ACHN and A-498. Furthermore, knockdown of ghrelin expression reduced in vitro migration and in vivo metastasis, suggesting a requirement for ghrelin accumulation in the microenvironment for RCC metastasis. Analysis of microarray signatures using Ingenuity Pathway Analysis (IPA) and MetaCore pointed to the potential regulation by ghrelin of Snail, a transcriptional repressor of E-cadherin. We further observed that Ghrelin increased the expression, nuclear translocation and promoter-binding activity of Snail. Snail silencing blocked the ghrelin-mediated effects on E-cadherin repression and cell migration. Snail-E-cadherin regulation was mediated by GHS-R-triggered Akt phosphorylation at Ser473 and Thr308. Pretreatment with PI3K inhibitors, LY294002 and wortmannin, as well as Akt siRNA, decreased ghrelin-induced Akt phosphorylation, Snail promoter binding activity and migration. Taken together, our findings indicate that ghrelin can activate Snail function via the GHS-R-PI3K-Akt axis, which may contribute to RCC metastasis. The microarray raw data were retrieved from the Cancer Genome Atlas (TCGA) [KIRC gene expression (IlluminaHiSeq) dataset].

Lin TC ，Liu YP ，Chan YC ，Su CY ，Lin YF ，Hsu SL ，Yang CS ，Hsiao M ... -  《-》

microRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis.

Wang X ，Chen X ，Wang R ，Xiao P ，Xu Z ，Chen L ，Hang W ，Ruan A ，Yang H ，Zhang X ... -  《-》

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 ... -  《-》

The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma.

Doberstein K ，Pfeilschifter J ，Gutwein P 《-》

TNF-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a GSK3β-dependent mechanism.

Ho MY ，Tang SJ ，Chuang MJ ，Cha TL ，Li JY ，Sun GH ，Sun KH ... -  《-》