CCL18 is a member of CCL chemokines and is frequently overexpressed in cancer. Elevated CCL18 expression has been reported to be associated with poor prognosis of gastric cancer. However, the molecular mechanisms of CCL18 in gastric cancer cells remain elusive. In our study, we found that CCL18 was highly expressed in different gastric cancer cells. CCL18 stimulation dose-dependently enhanced the invasion and migration of MGC-803 cells. Knockdown of endogenous CCL18 inhibited the invasion and migration of MGC-803 cells, whereas overexpression of CCL18 promoted the invasion and migration of MKN28 cells. We further found that CCL18 increased the expressions of MMP-3 and Slug and decreased the expression of E-cadherin in MGC-803 cells. In addition, CCL18 time-dependently induced activation of ERK1/2, IκBα, and NF-κB. These effects of CCL18 were prevented by ERK1/2 selective inhibitor U0126 as well as NF-κB selective inhibitor BAY117082. Taken together, our findings establish a signaling role for CCL18 in gastric cancer cells and identify that the CCL18/ERK1/2/NF-κB signaling pathway is essential for tumor invasiveness in gastric cancer cells. Thus, our data may provide knowledge for using CCL18 as a novel target for effective diagnosis and treatment of gastric cancer.
Keywords: CCL18; ERK1/2; Gastric cancer; Invasion; Migration; NF-κB.