Expression of Snail was significantly increased with AQP3 over-expression, and decreased with AQP3 down-regulation. Phosphorylation of AKT was significantly inhibited by LY294002 in cells treated with EGF. Inhibition of p-AKT by LY294002 attenuated AQP3-induced Snail expression in cells. This initial study provides evidence that the PI3K/AKT/Snail signaling pathway is likely involved in selleck compound AQP3-mediated EMT of human GC cells. Figure 6 AQP3 regulates EMT via the PI3K/AKT/Snail pathway. SGC7901and

MGC803 cells were treated with control siRNA, RNAi AQP3 and EGF, with or without a PI3K/AKT inhibitor. Proteins were analyzed by western blotting assay. GAPDH was used as an internal control. The relative accumulation of proteins was compared with the untreated group. Discussion AQP3 has been established as a critical determinant of tumor growth and spread of human GC in

previous studies. It has been speculated to promote GC cell migration and metastasis by inducing EMT. We found that AQP3 was up-regulated, and E-cadherin was repressed in cancer tissues. Vimentin immunoactivity was observed in 14 carcinoma tissues where AQP3 was overexpressed and E-cadherin was lacking. Over-expression of AQP3 correlated with repression of E-cadherin, and expression of vimentin. Loss of E-cadherin is regarded as a key step of EMT [24], while vimentin is a marker of mesenchymal differentiation find more Galeterone [25]. EMT is thought to be transient and occurs during progression towards metastases in several types of solid tumors [22]. Our findings suggest that AQP3 is associated with EMT induction in human GC cases. With respect to the clinical significance of AQP3 over-expression, E-cadherin repression, and vimentin expression, we showed that they were all associated with lymphovascular invasion. In particular, AQP3 and E-cadherin were associated with lymph node metastasis, while

AQP3 and vimentin were associated with Lauren classification, and E-cadherin was associated with depth of tumor invasion. Patients with AQP3 over-expression exhibited worse OS compared with those lacking AQP3 expression. Repression of E-cadherin, and vimentin expression predicted poor prognosis for GC. These results are consistent with those reported by Zhou [25] and Corso [26]. However, our findings demonstrate for the first time the role of AQP3 in the prognosis of patients with GC. Our previous results have shown that AQP3 promotes GC cell proliferation and migration. Because EMT of tumor cells is accepted to be closely associated with cancer invasion and metastasis [10, 11], we investigated the effects of AQP3 on GC cell proliferation, migration, and invasion using EdU incorporation assays and transwell assays. AQP3 over-expression enhanced cell proliferation, migration and invasion, implying that AQP3 has a role in facilitating GC progression.