S100A9 promotes the proliferation and invasion of HepG2 hepatocellular             carcinoma cells via the activation of the MAPK signaling pathway.
The S100A9 protein, a member of the S100 protein family, is often upregulated in various types of cancer, including hepatocellular carcinoma (HCC). S100A9 acts as a danger signal when secreted to the extracellular space and is thought to play an important role during tumorigenesis. Despite this fact, little is known about the effects of S100A9 in the tumor microenvironment on HCC. Therefore, in this study, we investigated the effects of exogenous S100A9 on the proliferation and invasion of HepG2 HCC cells, as well as the molecular mechanisms underlying these effects. Our results demonstrated that exogenous S100A9 promoted the proliferation, clone formation and invasion of HepG2 cells in vitro, as shown by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltrazolium bromide (MTT), clone formation and transwell invasion assays, respectively, and also promoted tumor growth in vivo by tumorigenicity assays in nude mice. Furthermore, S100A9 increased the phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases (MAPKs) in HepG2 cells. When the phosphorylation of p38 was inhibited by SB203580 (a p38 inhibitor), the S100A9-induced cell invasion was reversed; when the phosphorylation of ERK1/2 was inhibited by PD98059 (an ERK1/2 inhibitor), the S100A9-induced cell proliferation was reversed. These data suggest that the S100A9-induced proliferation and invasion of HepG2 cells are partly mediated by the activation of the MAPK signaling pathway.
Department of Laboratory Medicine, Chongqing Medical University,                     Chongqing 400016, P.R. China.
Rui
R
Wu
Liang
L
Duan
Liwei
L
Ye
Haiyang
H
Wang
Xia
X
Yang
Yunyuan
Y
Zhang
Xian
X
Chen
Yan
Y
Zhang
Yaguang
Y
Weng
Jingyong
J
Luo
Min
M
Tang
Qiong
Q
Shi
Tongchuan
T
He
Lan
L
Zhou
D000818:Animals; D040502:Calgranulin B / Q000494:pharmacology / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D013778:Tetrazolium Salts; D013844:Thiazoles; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D040502:Calgranulin B; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013778:Tetrazolium Salts; D013844:Thiazoles; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C022616:thiazolyl blue; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one