Connective tissue growth factor enhances the migration of gastric cancer through downregulation of E-cadherin via the NF-κB pathway

Local invasion and distant metastasis are difficult problems for surgical intervention and treatment in gastric cancer. Connective tissue growth factor (CTGF/CCN2) was considered to have an important role in this process. In this study, we demonstrated that expression of CTGF was significantly upregulated in clinical tissue samples of gastric carcinoma (GC) samples. Forced expression of CTGF in AGS GC cells promoted their migration in culture and significantly increased tumor metastasis in nude mice, whereas RNA interference-mediated knockdown of CTGF in GC cells significantly inhibited cell migration in vitro. We disclose that CTGF downregulated the expression of E-cadherin through activation of the nuclear factor-kappa appa B (NF-kappa B) pathway. The effects of CTGF in GC cells were abolished by dominant negative I kappa appaB. Collectively, these data reported here demonstrate CTGF could modulate the NF-kappa appaB pathway and perhaps be a promising therapeutic target for gastric cancer invasion and metastasis. (Cancer Sci 2011; 102: 104-110).