title: 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. Compared with matched primary HCC, higher expression of EIF5A2 protein was observed in 25/47 (53.2%) of metastatic tumors. Functional studies found that ectopic expression of EIF5A2 could enhance cancer cell migration and invasion in vitro and tumor metastasis in vivo in an experimental mouse model. Moreover, inhibition of EIF5A by small interfering RNA (siRNA) or deoxyhypusine synthase (DHPS) inhibitor GC7, which inhibits EIF5A2 maturation, could effectively decrease cell motility. Further study found that EIF5A2 was able to induce epithelial-mesenchymal transition (EMT), a key event in tumor invasion and metastasis, characterized by down-regulation of epithelial markers (E-cadherin and beta-catenin) and up-regulation of mesenchymal markers (fibronectin, N-cadherin, alpha-SMA, and vimentin). In addition, EIF5A2 could also activate RhoA/Rac1 to stimulate the formation of stress fiber and lamellipodia.
  
  
  CONCLUSIONS
  EIF5A2 plays an important role in HCC invasion and metastasis by inducing EMT, as well as stimulating cytoskeleton rearrangement through activation of RhoA and Rac1.
authors.affiliation: Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China.
authors.forename: Dong-Jiang
authors.initials: DJ
authors.lastname: Tang
authors.forename: Sui-Sui
authors.initials: SS
authors.lastname: Dong
authors.forename: Ning-Fang
authors.initials: NF
authors.lastname: Ma
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Leilei
authors.initials: L
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Sze Hang
authors.initials: SH
authors.lastname: Lau
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000556:secondary*; D002465:Cell Movement; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors / Q000235:genetics; D010448:Peptide Initiation Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: C100667:N(1)-guanyl-1,7-diaminoheptane; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; C425967:eIF-5A2; D006147:Guanine; D000587:Oxidoreductases Acting on CH-NH Group Donors; C063507:deoxyhypusine synthase; D020741:rho GTP-Binding Proteins