title: c-Met upregulates aquaporin 3 expression in human gastric carcinoma cells via the ERK signalling pathway.
abstract: Aquaporin 3 (AQP3) and c-Met are both overexpressed in human gastric carcinoma and highly associated with its metastasis and invasion. However, it still remains unknown whether c-Met and AQP3 correlate with each other. Herein, we demonstrated that c-Met expression in gastric cancer tissues significantly correlated with differentiation, lymph node metastasis and lymphovascular invasion, and c-Met exhibited marked association with AQP3 expression. Immunoblotting assays showed that hHGF phosphorylated c-Met in SGC7901 and AGS cells and upregulated AQP3 expression in a dose- or time-dependent way. RNAi against c-Met reduced total c-Met levels by about two thirds in both AGS and SGC7901 cells and attenuated hHGF-induced AQP3 expression significantly. In vitro migration and proliferation assays showed that siRNA against AQP3 noticeably restrained HGF-promoted migration and proliferation of these cells. Furthermore, Immunoblotting studies revealed that HGF induced phosphorylation of ERK, and pre-treatment with U0126, a MAPK/ERK inhibitor, partially inhibited hHGF-induced increase in AQP3 expression. Together, these data provide initial evidence that c-Met regulates the expression of AQP3 via the ERK signalling pathway in gastric carcinoma. These findings assist in understanding the mechanism of growth and invasion of gastric carcinoma, and provide a possible strategy for the inhibition of gastric tumor metastasis.
authors.affiliation: Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Gui
authors.forename: Longying
authors.initials: L
authors.lastname: Deng
authors.forename: Maocai
authors.initials: M
authors.lastname: Sun
authors.forename: Renhua
authors.initials: R
authors.lastname: Guo
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhang
authors.forename: Lizong
authors.initials: L
authors.lastname: Shen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D051400:Aquaporin 3 / Q000378:metabolism*; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D009363:Neoplasm Proteins; D051400:Aquaporin 3; D019859:Proto-Oncogene Proteins c-met