title: Role of EIF5A2, a downstream target of Akt, in promoting melanoma cell invasion.
abstract: BACKGROUND
  Cutaneous melanoma is a life-threatening skin cancer because of its poorly understood invasive nature and high metastatic potential. This study examines the importance of eukaryotic translation initiation factor 5A2 (EIF5A2) in melanoma pathogenesis.
  
  
  METHODS
  We examined EIF5A2 expression in 459 melanocytic lesions using tissue microarray. In addition, melanoma cell lines were subjected to invasion and cell proliferation assays, zymography, FACS and real-time PCR to investigate the role of EIF5A2 in cancer progression.
  
  
  RESULTS
  Positive EIF5A2 staining increased from dysplastic naevi to primary melanomas (PMs; P=0.001), and further increased in metastatic melanomas (P=0.044). Eukaryotic translation initiation factor 5A2 expression was correlated with melanoma thickness (P<0.001) and was inversely correlated with the 5-year survival of PM patients especially those with tumour ≤2 mm thick. Strikingly, none of the latter died within 5 years in EIF5A2-negative staining group. Cox regression analysis revealed that EIF5A2 is an independent prognostic marker. Further, we found that EIF5A2 is a novel downstream target of phosphorylated Akt. Both melanoma cell invasion and MMP-2 activity increased and decreased with EIF5A2 overexpression and knockdown, respectively.
  
  
  CONCLUSIONS
  We for the first time showed that EIF5A2, as a target of PI3K/Akt, promotes melanoma cell invasion and may serve as a promising prognostic marker and a potential therapeutic target for melanoma.
authors.affiliation: Department of Dermatology and Skin Science, Research Pavilion, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Khosravi
authors.affiliation: Department of Dermatology and Skin Science, Research Pavilion, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: R P C
authors.initials: RP
authors.lastname: Wong
authors.affiliation: Department of Dermatology and Skin Science, Research Pavilion, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: G S
authors.initials: GS
authors.lastname: Ardekani
authors.affiliation: Department of Dermatology and Skin Science, Research Pavilion, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Martinka
authors.affiliation: Department of Surgery, Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: C J
authors.initials: CJ
authors.lastname: Ong
authors.affiliation: Department of Dermatology and Skin Science, Research Pavilion, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D014408:Biomarkers, Tumor; D020778:Matrix Metalloproteinase 2; D010448:Peptide Initiation Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A