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Mol. Cells 2013; 35(3): 226-234

Published online February 26, 2013

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

© The Korean Society for Molecular and Cellular Biology

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

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

Department of Pathology, Cancer Research Institute, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Korea

Received: October 15, 2013; Revised: January 28, 2013; Accepted: January 28, 2013

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.

Keywords gastric cancer cells, MMP, NF-κB, p38MAPK, S100A8/A9

Article

Research Article

Mol. Cells 2013; 35(3): 226-234

Published online March 31, 2013 https://doi.org/10.1007/s10059-013-2269-x

Copyright © The Korean Society for Molecular and Cellular Biology.

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

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

Department of Pathology, Cancer Research Institute, Pusan National University Hospital and Pusan National University School of Medicine, and Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Korea

Received: October 15, 2013; Revised: January 28, 2013; Accepted: January 28, 2013

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.

Keywords: gastric cancer cells, MMP, NF-κB, p38MAPK, S100A8/A9

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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