Wang Haiyan, Duan Liang, Zou Zhengyu, Li Huan, Yuan Shimei, Chen Xian, Zhang Yunyuan, Li Xueru, Sun Hui, Zha He, Zhang Yan, Zhou Lan
1. Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China;
2. Department of Laboratory, the First People's Hospital of Jiulongpo District, Chongqing 400050, China.
Int J Med Sci. 2014 Jun 8;11(8):841-9. doi: 10.7150/ijms.8128. eCollection 2014.
The S100 protein family member S100A4 regulates various cellular functions. Previous studies have shown that elevated expression of S100A4 is associated with progression and metastasis of colorectal cancer (CRC). However, little is known about whether and how S100A4 contributes to CRC development. In our present study, the elevated expression of S100A4 in CRC tissues compared to matched adjacent normal tissues was confirmed by immunohistochemistry, semi-quantitative RT-PCR and Western blot. Adenovirus-mediated S100A4 overexpression obviously enhanced viability and migration of CRC cells, which was detected by MTT assay and transwell assay, respectively. Additionally, S100A4 overexpression increased the phosphorylation levels of Akt, mTOR and p70S6K. These effects of S100A4 were abolished by treatment with either the specific PI3K/Akt inhibitor LY294002, or the specific mTOR/p70S6K inhibitor rapamycin. Furthermore, overexpression of S100A4 resulted in upregulation of VEGF and downregulation of E-cadherin, which were strongly reversed by either LY294002 or rapamycin. Altogether, our results demonstrate that activation of the PI3K/Akt/mTOR/p70S6K signaling pathway is involved in S100A4-induced viability, migration, upregulation of VEGF and downregulation of E-cadherin in CRC cells.
S100蛋白家族成员S100A4可调节多种细胞功能。先前的研究表明，S100A4表达升高与结直肠癌（CRC）的进展和转移相关。然而，关于S100A4是否以及如何促进CRC发展知之甚少。在我们目前的研究中，通过免疫组织化学、半定量RT-PCR和蛋白质印迹法证实，与匹配的相邻正常组织相比，CRC组织中S100A4表达升高。腺病毒介导的S100A4过表达分别通过MTT法和Transwell法检测，明显增强了CRC细胞的活力和迁移能力。此外，S100A4过表达增加了Akt、mTOR和p70S6K的磷酸化水平。用特异性PI3K/Akt抑制剂LY294002或特异性mTOR/p70S6K抑制剂雷帕霉素处理可消除S100A4的这些作用。此外，S100A4过表达导致VEGF上调和E-钙黏蛋白下调，而LY294002或雷帕霉素可强烈逆转这些变化。总之，我们的结果表明，PI3K/Akt/mTOR/p70S6K信号通路的激活参与了S100A4诱导的CRC细胞活力、迁移、VEGF上调和E-钙黏蛋白下调。
