Abstract 5119: Overexpression of EIF5A2 enhances cell motility and promotes HCC metastasis through Rho and Rac signaling pathways

Abstract

Abstract Hepatocellular carcinoma is characterized by its high incidence of tumor recurrence and metastasis; however, the underlying molecular mechanisms are largely unknown. In the present study, a novel metastasis-related gene, EIF5A2, was characterized for its role in HCC metastasis and underlying molecular mechanism. Overexpression of EIF5A2 mRNA was detected in 50/81(61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. Compared with matched primary HCC, higher expression of EIF5A2 protein was observed in 25/47 (53.2%) metastatic tumors. In vitro assays showed that ectopic expression of EIF5A2 could enhance cancer cell migration and invasion, and experimental mouse model demonstrated that over expression of EIF5A2 promoted tumor metastasis in vivo. Moreover, inhibition of EIF5A2 by siRNA or deoxyhypusine synthase (DHPS) inhibitor GC7, which inhibits EIF5A2 maturation, could effectively decrease cell motility. Further study found that EIF5A2 could activate RhoA/Rac1 to stimulate the formation of stress fiber and lamellipodia. The rearrangement of cytoskeleton further induced epithelial-mesenchymal transition (EMT), a key event in tumor invasion and metastasis, characterized by downregulation of epithelial markers (E-cadherin and β-catenin) and upregulation of mesenchymal markers (fibronectin, N-cadherin, α-SMA and vimentin). Moreover, the activation of Rho GPases by overexpression of EIF5A2 also influenced cell cycle progression. Conclusions: EIF5A2 promotes HCC invasion and metastasis by stimulating cytoskeleton rearrangement through activation of RhoA and Rac1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5119.