Elsevier

Molecules and Cells

Volume 35, Issue 3, March 2013, Pages 226-234
Molecules and Cells

S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

https://doi.org/10.1007/s10059-013-2269-xGet rights and content
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S100A8 and S100A9 (S100A8/A9) are low-molecular weight members of the S100 family of calcium-binding proteins. Recent studies have reported S100A8/A9 promote tumorigenesis. We have previously reported that S100A8/A9 is mostly expressed in stromal cells and inflammatory cells between gastric tumor cells. However, the role of environmental S100A8/A9 in gastric cancer has not been defined. We observed in the present study the effect of S100A8/A9 on migration and invasion of gastric cancer cells. S100A8/ A9 treatment increased migration and invasionat lower concentrations that did not affect cell proliferation and cell viability. S100A8/A9 caused activation of p38 mitogen activated protein kinase (MAPK) and nuclear factor-κΒ (NF-KB). The phosphorylation of p38 MAPK was not affected by the NF-KB inhibitor Bay whereas activation of NF-KB was blocked by p38 MAPK inhibitor SB203580, indicating that S100A8/A9-induced NF-KB activation is mediated by phosphorylation of p38 MAPK. S100A8/A9-induced cell migration and invasion was inhibited by SB203580 and Bay, suggesting that activation of p38 MAPK and NF-KB is involved in the S100A8/A9 induced cell migration and invasion. S100A8/A9 caused an increase in matrix metalloproteinase 2 (MMP2) and MMP12 expression, which were inhibited by SB203580 and Bay. S100A8/A9-induced cell migration and invasion was inhibited by MMP2 siRNA and MMP12 siRNA, indicating that MMP2 and MMP12 is related to the S100A8/A9 induced cell migration and invasion. Taken together, these results suggest that S100A8/A9 promotes cell migration and invasion through p38 MAPK-dependent NF-KB activation leading to an increase of MMP2 and MMP12 in gastric cancer.

Keywords

gastric cancer cells
MMP
NF-κΒ
p38MAPK
S100A8/A9

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