title: Knockdown of WAVE3 impairs HGF induced migration and invasion of prostate cancer cells.
abstract: BACKGROUND
  The WASP (Wiskott-Aldrich syndrome protein) and WAVE (WASP Verpolin homologous) family of proteins are structurally related and responsible for regulation of actin polymerization through their interaction with actin related proteins 2&3 (ARP 2/3). WAVE-3 has exhibited an association with disease progression and poorer prognosis of certain malignancies. In the current study, we determined the role of WAVE-3 in hepatocyte growth factor induced cellular changes including cell matrix interaction, invasion and cellular motility, and pathways that may be responsible for the changes in prostate cancer cells.
  
  
  METHODS
  We used hammer head ribozymes to knock down the expression of WAVE-3 in PC-3 prostate cancer cell line. In vitro cellular functional assays including growth, invasion, adhesion, motility and invasion, were performed to assess the effects of WAVE-3 knock down. Further experimentation was performed to investigate the role of different pathway through expression and phosphorylation status of various intermediate proteins.
  
  
  RESULTS
  WAVE-3 knockdown reduced invasive potential and motility of prostate cancer cells. Following addition of HGF, control cells showed significantly increased invasion and motility (p value <0.5) and marked increase in cellular growth. However, WAVE-3 knockdown cell line failed to show any increase in these trends (p value <0.5) except increased growth compared with control cells. Further experiments revealed that HGF-induced activation of Paxillin was weakened by the knockdown of WAVE-3. Our study also indicated that reduced invasiveness following WAVE-3 knockdown, may be related to reduce activity of MMP-2.
  
  
  CONCLUSIONS
  Our studies suggest a vital role of WAVE-3 in HGF induced invasion and migration in which Paxillin and MMP-2 are involved. Further study will shed light on its potential as therapeutic target to suppress local invasion and metastasis of prostate cancer cells.
authors.affiliation: Metastasis & Angiogenesis Research Group, Department of Surgery, Institute of Cancer and Genetics, Cardiff, UK.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Moazzam
authors.affiliation: Metastasis & Angiogenesis Research Group, Department of Surgery, Institute of Cancer and Genetics, Cardiff, UK ; Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.affiliation: Metastasis & Angiogenesis Research Group, Department of Surgery, Institute of Cancer and Genetics, Cardiff, UK ; Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN UK.
authors.forename: Ping-Hui
authors.initials: PH
authors.lastname: Sun
authors.affiliation: Metastasis & Angiogenesis Research Group, Department of Surgery, Institute of Cancer and Genetics, Cardiff, UK.
authors.forename: Howard
authors.initials: H
authors.lastname: Kynaston
authors.affiliation: Metastasis & Angiogenesis Research Group, Department of Surgery, Institute of Cancer and Genetics, Cardiff, UK ; Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
keywords: HGF; Invasion and migration; Prostate cancer; WAVE3