c-Met upregulates aquaporin 3 expression in human gastric carcinoma cells via the ERK signalling pathway.

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.
AuthorsJianping Wang, Zhifu Gui, Longying Deng, Maocai Sun, Renhua Guo, Weiming Zhang, Lizong Shen
JournalCancer letters (Cancer Lett) Vol. 319 Issue 1 Pg. 109-17 (Jun 1 2012) ISSN: 1872-7980 [Electronic] Ireland
PMID22261330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Neoplasm Proteins
  • Aquaporin 3
  • Proto-Oncogene Proteins c-met
  • Adenocarcinoma (metabolism, pathology)
  • Aquaporin 3 (metabolism)
  • Female
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • Neoplasm Proteins (metabolism)
  • Proto-Oncogene Proteins c-met (metabolism)
  • Stomach Neoplasms (metabolism, pathology)
  • Up-Regulation

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