title: EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo.
abstract: BACKGROUND
  EIF5A2, eukaryotic translation initiation factor 5A2, is associated with several human cancers. In this study, we investigated the role of EIF5A2 in the metastatic potential of localised invasive bladder cancer (BC) and its underlying molecular mechanisms were explored.
  
  
  METHODS
  The expression pattern of EIF5A2 in localised invasive BC was determined by immunohistochemistry. In addition, the function of EIF5A2 in BC and its underlying mechanisms were elucidated with a series of in vitro and in vivo assays.
  
  
  RESULTS
  Overexpression of EIF5A2 was an independent predictor for poor metastasis-free survival of localised invasive BC patients treated with radical cystectomy. Knockdown of EIF5A2 inhibited BC cell migratory and invasive capacities in vitro and metastatic potential in vivo and reversed epithelial-mesenchymal transition (EMT), whereas overexpression of EIF5A2 promoted BC cells motility and invasiveness in vitro and metastatic potential in vivo and induced EMT. In addition, we found that EIF5A2 might activate TGF-β1 expression to induce EMT and drive aggressiveness in BC cells. EIF5A2 stabilized STAT3 and stimulated nuclear localisation of STAT3, which resulted in increasing enrichment of STAT3 onto TGF-β1 promoter to enhance the transcription of TGF-β1.
  
  
  CONCLUSIONS
  EIF5A2 overexpression predicts tumour metastatic potential in patients with localised invasive BC treated with radical cystectomy. Furthermore, EIF5A2 elevated TGF-β1 expression through STAT3 to induce EMT and promotes aggressiveness in BC.
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: J-H
authors: JH
authors: Wei
authors: 1] Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China [2] Department of Urology, Jiangmen Hospital, Sun Yat-Sen University, Jiangmen, China.
authors: J-Z
authors: JZ
authors: Cao
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: D
authors: D
authors: Zhang
authors: Department of Pathology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: B
authors: B
authors: Liao
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: W-M
authors: WM
authors: Zhong
authors: Department of Urology, Jiangmen Hospital, Sun Yat-Sen University, Jiangmen, China.
authors: J
authors: J
authors: Lu
authors: Department of Urology, Yuhuangding Hospital, Qingdao University Medical College, Yantai, China.
authors: H-W
authors: HW
authors: Zhao
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: J-X
authors: JX
authors: Zhang
authors: Department of Urology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
authors: Z-T
authors: ZT
authors: Tong
authors: Department of Urology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
authors: S
authors: S
authors: Fan
authors: Department of Urology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
authors: C-Z
authors: CZ
authors: Liang
authors: Department of Urology, Jiangmen Hospital, Sun Yat-Sen University, Jiangmen, China.
authors: Y-B
authors: YB
authors: Liao
authors: Department of Urology, Jiangmen Hospital, Sun Yat-Sen University, Jiangmen, China.
authors: J
authors: J
authors: Pang
authors: Department of Urology, Jiangmen Hospital, Sun Yat-Sen University, Jiangmen, China.
authors: R-H
authors: RH
authors: Wu
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Y
authors: Y
authors: Fang
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Z-H
authors: ZH
authors: Chen
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: B
authors: B
authors: Li
authors: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors: D
authors: D
authors: Xie
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: W
authors: W
authors: Chen
authors: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: J-H
authors: JH
authors: Luo
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010448:Peptide Initiation Factors / Q000378:metabolism*; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D014408:Biomarkers, Tumor; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor; D053773:Transforming Growth Factor beta1; D000097574:Eukaryotic Translation Initiation Factor 5A; C494086:STAT3 protein, human