title: P21-activated kinase-2 is a critical mediator of transforming growth factor-β-induced hepatoma cell migration.
abstract: OBJECTIVE
  Transforming growth factor-β (TGF-β) has been shown to play a central role in the promotion of cell motility, but its functional mechanism has remained unclear. With the aim of investigating the diagnostic and treatment modalities for patients with hepatocellular carcinoma (HCC), the signaling pathway that may contribute to TGF-β-mediated cell invasion in hepatoma cells was evaluated.
  
  
  METHODS
  Three hepatoma cell lines, HepG2, PLC/PRF/5, and HLF, were treated with TGF-β, and the involvement of the non-canonical TGF-β pathway was analyzed by cell migration assays. HepG2 cells were treated with a p21-activated kinase-2 (PAK2)-targeting small interfering RNA and analyzed for their cell motility. The relationships between the PAK2 status and the clinicopathological characteristics of 62 HCC patients were also analyzed.
  
  
  RESULTS
  The cell migration assays showed that Akt is a critical regulator of TGF-β-mediated cell migration. Western blotting analyses showed that TGF-β stimulated Akt and PAK2 in all three hepatoma cell lines, and phosphorylated PAK2 was blocked by Akt inhibitor. Suppression of PAK2 expression by small interfering RNA resulted in increased focal adhesions with significantly repressed cell migration in the presence of TGF-β. Clinicopathological analyses showed that the phosphorylation level of PAK2 was closely associated with tumor progression, metastasis, and early recurrence of HCC.
  
  
  CONCLUSIONS
  PAK2 may be a critical mediator of TGF-β-mediated hepatoma cell migration, and may represent a potential target for the treatment of HCC.
authors: Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors: Munehiro
authors: M
authors: Sato
authors: Yasunobu
authors: Y
authors: Matsuda
authors: Toshifumi
authors: T
authors: Wakai
authors: Masayuki
authors: M
authors: Kubota
authors: Mami
authors: M
authors: Osawa
authors: Shun
authors: S
authors: Fujimaki
authors: Ayumi
authors: A
authors: Sanpei
authors: Masaaki
authors: M
authors: Takamura
authors: Satoshi
authors: S
authors: Yamagiwa
authors: Yutaka
authors: Y
authors: Aoyagi
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002465:Cell Movement; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured; D054462:p21-Activated Kinases / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta; D054462:p21-Activated Kinases