Tumor Biology

, Volume 37, Issue 1, pp 641–651 | Cite as

CCL18 promotes the invasion and migration of gastric cancer cells via ERK1/2/NF-κB signaling pathway

Original Article

Abstract

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 Gastric cancer Invasion Migration ERK1/2 NF-κB 

Notes

Conflicts of interest

None

Supplementary material

13277_2015_3825_Fig9_ESM.gif (67 kb)
Supplementary Fig. 1

MGC-803 cells were treated with CCL18 of different times as indicated. a The expression of phosphor-ERK1/2 was detected by western blot. b The transcriptional activity of NF-κB was measured by NF-κB activity assay. Results shown are representatives of three independent experiments, *p < 0.05. (GIF 67 kb)

13277_2015_3825_MOESM1_ESM.tif (303 kb)
High resolution image (TIFF 303 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of General SurgeryThe First Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Department of GeriatricsThe Heilongjiang Provincial HospitalHarbinChina

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