S100P increases Twist1 and ZEB1 expression and triggers FAK/AKT signaling in lung cancer

• Main Authors: Yung-Yu Liang, 梁詠瑜
• Other Authors: Ya-Ling Hsu
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/2hcdq8

碩士 === 高雄醫學大學 === 醫學研究所-基礎醫學組 === 102 === Lung cancer accounts for 12% of all new cases of cancers worldwide and is the leading cause of cancer-related death. S100P, a calcium binding protein, has been reported to involve in cancer metastasis. However, the role of S100P is poorly known in lung cancer. This study first reports that S100P enhances the migration and invasion ability of lung cancer cells through the Twist1/ZEB1 upregulation and FAK (focal adhesion kinase)/Src/AKT signaling pathway. Compared to low invasive CL1-0 lung cancer cells, the expression of S100P was greater expression than that of high invasive CL1-5 lung cancer cells. Overexpression of S100P increased the migration, invasion and epithelial-mesenchymal transition (EMT) in CL1-0 cells, whereas knockdown of S100P expression decreased the migration, invasion and EMT in CL1-5 cells. Enhancement of S100P expression triggered FAK activation, which in turn increased the activation of Src and AKT signaling. Blockade of FAK and AKT by specific inhibitors prevented S100P-mediated cell migration and invasion. On the other hand, S100P also increased Twist1 and ZEB1 expressions, which are responsible for EMT in lung cancer. Knockdown of Twist1 and ZEB1 by siRNA inhibited S100P-mediated cell migration. S100P also promoted lung cancer metastasis in vivo animal model. More importantly, elevated expression of S100P protein is also found in human lung cancer specimen. This study demonstrates that S100P may be a novel anticancer for the prevention of non-small cell lung cancer metastasis. It can also be a biomarker for prognosis of lung cancer metastasis.