Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma†

Abstract

A high incidence of tumor recurrence and metastasis has been reported in hepatocellular carcinoma (HCC) patients; however, the underlying molecular mechanisms are largely unknown. In the present study a novel metastasis-related gene, eukaryotic initiation factor 5A2 (EIF5A2), was characterized for its role in HCC metastasis and underlying molecular mechanisms. Overexpression of EIF5A2 messenger RNA (mRNA) was detected in 50/81 (61.7%) of HCCs, which was significantly higher than those in nontumorous liver tissues. A worldwide increase in mortality associated with hepatocellular carcinoma (HCC) has recently been reported. 1,2 Clinical treatment of HCC remains challenging due to a high incidence of tumor recurrence. The main cause of death in HCC patients is intrahepatic metastasis but the underlying mechanisms are still not fully understood. It is generally believed that to give rise to a metastatic tumor, cancer cells from a primary site must complete all of the following steps: invasion, intravasation, survival and arrest in the blood stream, extravasation, and colonization at a new site. The motility of cancer cells, driven by the actin cytoskeleton network, has been well documented to play crucial roles at multiple steps during the metastasis process.

Biological Relevance and Therapeutic Potential of the Hypusine Modification System

“…The eIF-5A2 gene is located on 3q26, a chromosomal region that is frequently amplified in cancer. Moreover, the expression of eIF-5A2 in those entities correlates with survival (77,78), disease stage, as well as metastasis (79), suggesting that eIF-5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis. As eIF-5A2 shares almost 84% homology with eIF-5A1, it can be speculated that eIF-5A2 is also implicated in translation elongation and is responsible for the selective transport and translation of specific mRNA subsets.…”

Downregulation of the Notch signaling pathway inhibits hepatocellular carcinoma cell invasion by inactivation of matrix metalloproteinase-2 and -9 and vascular endothelial growth factor

“…The main cause of death in HCC patients is tumor progression with invasion and metastasis. However, the underlying mechanisms of HCC invasion and metastasis are still not fully understood (3). Thus, the discovery and subsequent development of novel agents to block HCC invasion and metastasis are primary research objectives for HCC.…”

Proteomic Characterization of Plasma Cells from Patients with Multiple Myeloma

“…Overexpression of eIF5A-2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through c-Myc to induce epithelial mesenchymal transition [63] and enhances cell motility and metastasis [64]. eIF5A-2 is an adverse prognostic marker of survival in stage I non-small cell lung cancer patients [65].…”