title: Requirement for FBP17 in invadopodia formation by invasive bladder tumor cells.
abstract: OBJECTIVE
  Invadopodia (protrusions of the plasma membrane formed by invasive tumor cells) have an essential role in bladder tumor invasion. To understand the process of bladder tumor invasion it is crucial to investigate the molecular mechanisms of invadopodia formation. We found that invasive bladder tumor cells express FBP17. In this study we examined the role of FBP17 in bladder tumor cell invadopodia formation and invasion.
  
  
  METHODS
  We used the 3 bladder tumor cell lines YTS-1, T24 and RT4 (ATCC®), and primary culture of bladder tumors from patients. Cells were stained with phalloidin for invadopodia formation. FBP17 knockdown cells were tested for invadopodia formation and subjected to invasion assay using a Transwell® cell culture chamber. We also examined the role of the extended FER-CIP4 homology and Src homology 3 domains of FBP17 in invadopodia formation in FBP17 mutant constructs.
  
  
  RESULTS
  Invadopodia formation was observed in invasive bladder tumor cells and FBP17 was localized to invadopodia in invasive cells. FBP17 knockdown decreased invadopodia formation in invasive cells to 13% to 14% (p <0.0005) and decreased their invasive capacity to 14% to 16% (p <0.001). The extended FER-CIP4 homology and Src homology 3 domains of FBP17 were necessary for invadopodia formation and invasion.
  
  
  CONCLUSIONS
  Invadopodia formation requires membrane deformation activity and recruitment of dynamin-2 mediated by FBP17. FBP17 has a critical role in the process of bladder tumor cell invasion by mediating invadopodia formation.
authors.affiliation: Department of Urology, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Mihoko
authors.initials: M
authors.lastname: Sutoh
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoneyama
authors.forename: Takuya
authors.initials: T
authors.lastname: Koie
authors.forename: Hisao
authors.initials: H
authors.lastname: Saitoh
authors.forename: Kanemitsu
authors.initials: K
authors.lastname: Yamaya
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Funyu
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuboi
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D002352:Carrier Proteins; C433770:FNBP1 protein, human; D050556:Fatty Acid-Binding Proteins