title: TGFBI-promoted adhesion, migration and invasion of human renal cell carcinoma depends on inactivation of von Hippel-Lindau tumor suppressor.
abstract: OBJECTIVE
  To investigate the role of transforming growth factor-β-induced (TGFBI) in metastasis of renal cell carcinoma (RCC) and the associations between TGFBI expression and von Hippel-Lindau (VHL) status.
  
  
  METHODS
  In null type VHL cells stably transfected with the VHL vector, the expression of VHL in cells with wild type VHL was decreased by siRNA. We investigated the effects of hypoxia-inducible transcription factor (HIF) on TGFBI in RCC cells by decreasing the expression levels of HIF-1α and HIF-2α through siRNA. The secretion of transforming growth factor-β1 (TGF-β1) in RCC cells with different VHL status was analyzed by enzyme-linked immunosorbent assay. The role of TGFBI in metastasis and the effect of VHL activation on TGFBI-induced adhesion, migration, and invasion in RCC cells were examined using matrigel, chemotaxis, and the transwell system, respectively.
  
  
  RESULTS
  Our results suggested that TGF-β1 and TGFBI might be targets of VHL, and the suppression of TGFBI by VHL is not by way of the HIF-1α or HIF-2α pathway. The expression of TGFBI was significantly enhanced by TGF-β1 in VHL-inactive RCC cells compared with VHL-active cells. In addition, these results indicate that TGFBI participated in the adhesion, migration, and invasion of RCC cells, which are dependent on the inactivation of VHL.
  
  
  CONCLUSIONS
  The results of the present study suggest that TGFBI-promoted metastasis of RCC cells depends on inactivation of the VHL tumor suppressor and that TGFBI could be a therapeutic target against RCC in the future.
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Donghao
authors.initials: D
authors.lastname: Shang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Liu
authors.forename: Peiqian
authors.initials: P
authors.lastname: Yang
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000503:physiopathology* / Q000556:secondary; D002448:Cell Adhesion / Q000502:physiology; D054443:Cell Migration Assays; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D020868:Gene Silencing; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000502:physiology*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1