Upregulation of Focal Adhesion Kinase by 14-3-3 epsilon via NF kappa B Activation in Hepatocellular Carcinoma

作者：Ko Bor Sheng; Jan Yee Jee; Chang Tzu Ching; Liang Shu Man; Chen Shyh Chang; Liu Tzu An; Wu Yao Ming; Wang John; Liou Jun Yang^*

来源：Anti-Cancer Agents in Medicinal Chemistry, 2013, 13(4): 555-562.

DOI：10.2174/1871520611313040004

• 14-3-3 epsilon
• Focal adhesion kinase
• Hepatocellular carcinoma
• Metastasis
• NF kappa B
• Survival

Focal adhesion kinase (FAK) is implicated in cancer cell survival, proliferation and migration. Expression of FAK expression is elevated and associated with tumor progression and metastasis in various tumors, including hepatocellular carcinoma (HCC). Increased 14-3-3 epsilon expression is shown to be a potential prognostic factor to predict higher risk of distant metastasis and worse overall survival in HCC. The aim of this study is to investigate whether FAK is associated or regulated by 14-3-3 epsilon to modulate tumor progression in HCC. In this study, 114 primary HCC tumors including 34 matched metastatic tumors were subjected to immunohistochemistry analysis of FAK and 14-3-3 epsilon expression. Overexpression of FAK was significantly associated with increased risk of extrahepatic metastasis (p=0.027) and reduced 5-year overall survival rate (p=0.017). A significant correlation of FAK and 14-3-3 epsilon expression was observed in primary tumor (p%26lt;0.001) and also metastatic tumors. Furthermore, overexpression of 14-3-3 epsilon induced FAK expression and promoter activity which were determined by Western blotting analysis and luciferase-reporter assay. Moreover, 14-3-3 epsilon enhanced NF kappa B activation and increased nuclear translocation of NF kappa B. Results from chromatin immunoprecipitation assay revealed that 14-3-3 epsilon induced NF kappa B binding on FAK promoter region. These findings suggest that FAK expression is correlated with and upregulated by 14-3-3 epsilon via activation of NF kappa B. Target to suppress or inactivate FAK alone, or combine with 14-3-3 epsilon is thus considered as the potential therapeutic strategy for preventing HCC tumor progression.

• 出版日期2013-5