The mechanisms underlying GC invasion and metastasis remain to be elucidated. GC invasion or metastasis is a multistep process that encompasses cancer cell invasion into surrounding tissues, entry into the systemic circulation, survival in the circulatory system, adhesion to endothelial cells, extravasation at distant organs, and the formation click here of secondary tumors [2, 3]. There is a growing understanding that epithelial-mesenchymal transition (EMT) contributes to invasion and metastasis [4–6]. The term EMT refers to a complex molecular and cellular process by which epithelial cells shed certain characteristics (such as cell-cell adhesion, planar and apical-basal polarity, and lack of motility),

and acquire mesenchymal features (motility, invasiveness, and

resistance to apoptosis) [7]. EMT plays key roles in embryonic development and is recognized as an important contributor to the pathogenesis of cancer and other human diseases [8, 9]. During EMT, expression levels of the CX-6258 mouse adhesion molecule E-cadherin are decreased, whereas N-cadherin and vimentin levels are increased. These molecular alterations possibly cause dysfunctional cell-cell adhesion and loss of cell-cell junctions, thereby allowing dissemination of tumor cells from the primary sites. It is widely accepted that EMT contributes to invasion, metastatic dissemination, and acquired resistance to therapy [10, 11]. Aquaporins (AQPs) are a family of small, integral membrane proteins that transport water and, in some cases, water and glycerol. Apart from these physiological functions [12], accumulating evidence further implicates the role of AQPs in cell migration

and proliferation [13–15]. Previously, we showed that GC tissues expressed higher levels of aquaporin 3 (AQP3) compared with that in normal mucosa. Additionally, AQP3 expression was associated with histological classification, lymph node metastasis, and lymphovascular invasion [16], indicating the involvement of AQP3 in the carcinogenesis and progression of GC. Human epidermal growth factor (EGF) [17] and hepatocyte growth factor (HGF) [18] up-regulate AQP3 expression via the extracellular signal-regulated kinase (ERK) pathway, then promote cell migration and proliferation Linifanib (ABT-869) in vitro, suggesting that AQP3 could be a potentially important determinant of tumor growth and the spread of GC. Little is known about the mechanisms of AQP3 with respect to GC invasion and metastasis. It is well understood that EMT can be induced by a large variety of stimuli during tumor progression [10]. Studies have shown that HGF and EGF can induce EMT in hepatocellular carcinoma and colon cancer Selleck mTOR inhibitor respectively [19, 20]. Recently, we showed that AQP3 positively regulates matrix metalloproteinases (MMPs) in GC cells [21], however up-regulation of MMPs is a characteristic of EMT [22]. We speculated that AQP3 might induce EMT and consequently promote GC cell migration and metastasis.