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Eur Rev Med Pharmacol Sci. 2014;18(9):1361-7.

S100A4 promotes squamous cell laryngeal cancer Hep-2 cell invasion via NF-kB/MMP-9 signal.

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  • 1Department of Head and Neck Tumor Surgery, Department of Radiotherapy, Linyi Cancer Institute Hospital, Linyi, China.



S100A4 is a member of the S100 family of calcium-binding proteins, which possesses a wide range of biological functions, such as regulation of angiogenesis, cell survival, motility, and invasion. Here, we demonstrate for the first time a major role of S100A4 in the cell invasion properties of the human laryngeal squamous carcinoma cells (LSCC) and evaluated the mechanism.


Cultured human LSCC cell line Hep-2 was overexpressed by transfection of pcDNA3.1-S100A4 plasmid. For this, cellular Hep-2 expression was quantified by Western blot analysis. Moreover, cell invasion and migration assays were performed. Furthermore, the impact of the S100A4 on NF-kB activity and MMP-9 expression was detected.


We found S100A4 potently promoted Hep-2 invasion, by increasing cell motility and matrix metalloproteinase-9 (MMP-9) production. The increase in MMP-9 production was mediated by activation of nuclear factor-kB transcriptional activity by S100A4. After MMP-9 and NF-kBp65 was inhibited by BB94 treatment and NF-kBp65 siRNA transfected, pcDNA3.1-S100A4 induced cell invasion and migration was decreased.


Our findings thus establish S100A4 as a major factor in the invasive abilities of Hep-2 cells.

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