S100A4通过NF-κB/MMP-9信号通路促进喉鳞状细胞癌Hep-2细胞的侵袭。

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

作者信息

Zhang W, Liu Y, Wang C-w

机构信息

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

出版信息

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

PMID:24867514

Abstract

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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

摘要

目的

S100A4是钙结合蛋白S100家族的成员，具有多种生物学功能，如调节血管生成、细胞存活、运动和侵袭。在此，我们首次证明S100A4在人喉鳞状癌细胞（LSCC）的细胞侵袭特性中起主要作用，并评估其机制。

材料与方法

通过转染pcDNA3.1-S100A4质粒使培养的人LSCC细胞系Hep-2过表达。为此，通过蛋白质印迹分析对细胞Hep-2表达进行定量。此外，进行细胞侵袭和迁移试验。此外，检测S100A4对NF-κB活性和MMP-9表达的影响。

结果

我们发现S100A4通过增加细胞运动性和基质金属蛋白酶-9（MMP-9）的产生，有力地促进了Hep-2的侵袭。MMP-9产生的增加是由S100A4激活核因子-κB转录活性介导的。在用BB94处理抑制MMP-9和NF-κBp65以及转染NF-κBp65 siRNA后，pcDNA3.1-S100A4诱导的细胞侵袭和迁移减少。