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S100A8 and S100A9 promotes invasion and migration through p38 mitogen-activated protein kinase-dependent NF-κB activation in gastric cancer cells

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Molecules and Cells

Abstract

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 mitogenactivated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The phosphorylation of p38 MAPK was not affected by the NF-κB inhibitor Bay whereas activation of NF-κB was blocked by p38 MAPK inhibitor SB203580, indicating that S100A8/A9-induced NF-κB 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-κB 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 MAPKdependent NF-κB activation leading to an increase of MMP2 and MMP12 in gastric cancer.

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Authors and Affiliations

  1. Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, Busan, 602-739, Korea

    Chae Hwa Kwon, Hyun Jung Moon, Hye Ji Park, Jin Hwa Choi & Do Youn Park

  2. Cancer Research Institute, Pusan National University Hospital and Pusan National University School of Medicine, Busan, 602-739, Korea

    Chae Hwa Kwon, Hyun Jung Moon, Hye Ji Park & Do Youn Park

  3. Biomedical Research Institute, Pusan National University Hospital, Busan, 602-739, Korea

    Chae Hwa Kwon & Do Youn Park

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  1. Chae Hwa Kwon
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Correspondence to Do Youn Park.

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Kwon, C.H., Moon, H.J., Park, H.J. et al. S100A8 and S100A9 promotes invasion and migration through p38 mitogen-activated protein kinase-dependent NF-κB activation in gastric cancer cells. Mol Cells 35, 226–234 (2013). https://doi.org/10.1007/s10059-013-2269-x

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  • DOI: https://doi.org/10.1007/s10059-013-2269-x

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