IL-6 induces AGS gastric cancer cell invasion via activation of the c-Src/RhoA/ROCK signaling pathway
Journal
International Journal of Cancer
Journal Volume
120
Journal Issue
12
Pages
2600-2608
Date Issued
2007
Author(s)
Abstract
Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of gastric cancer. Nonetheless, the underlying mechanism of how IL-6 promotes the spread of gastric cancer is still unclear. In this study, we used a modified Boyden chamber assay to test the invasion ability of different gastric cancer cell lines. Liposome-mediated transfection was used to introduce an IL-6 expression vector into AGS cells, and the transfectants were further examined for the expression of active RhoA and phosphorylated Src using a pull-down assay and coimmunoprecipitation/Western blot analysis. Furthermore, RhoA expression in gastric adenocarcinoma specimens was investigated immunohistochemically. We documented that IL-6 could promote AGS cell motility and invasiveness, and inhibition of RhoA expression by dominant negative RhoA, C3 transferase, or dominant negative Src expressing plasmids could effectively decrease the invasiveness of IL-6 transfectants. We also documented an interaction between active RhoA and phosphorylated-Src following IL-6 treatment. Gastric cancers displaying high expression of RhoA are highly correlated with aggressive lymph node metastasis, more advanced tumor stage, histologically diffuse type and poorer survival. In conclusion, IL-6 induces AGS gastric cancer cell invasion via activation of the c-Src/RhoA/ROCK signaling pathway and RhoA expression could be used as a prognostic factor in patients with gastric adenocarcinoma. ? 2007 Wiley-Liss, Inc.
SDGs
Other Subjects
exoenzyme C3; interleukin 6; liposome; RhoA guanine nucleotide binding protein; steroid receptor coactivator 1; adult; aged; article; cancer cell culture; cancer invasion; controlled study; expression vector; female; gene activation; genetic transfection; human; human cell; human tissue; immunohistochemistry; immunoprecipitation; lymph node metastasis; major clinical study; male; oncogene src; priority journal; protein phosphorylation; protein protein interaction; signal transduction; stomach adenocarcinoma; stomach cancer; Western blotting; Aged; Blotting, Western; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins pp60(c-src); Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; rhoA GTP-Binding Protein; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Stomach Neoplasms; Survival Analysis; Transfection
Type
journal article