title: Caveolin-1 induces lamellipodia formation via an Akt-dependent pathway.
abstract: BACKGROUND
  The enhancement of migration is critical for facilitating cancer cell metastasis.
  
  
  METHODS
  Lung cancer H23 cells were transfected with either a caveolin-1 (Cav-1) overexpression or shCav-1 plasmid and further subjected to cell migration assays and lamellipodia characterization. The regulation of Cav-1 via an ATP-dependent tyrosine kinase (Akt) pathway was further examined by Akt knockdown in Cav-1 overexpressing cells and migratory behavior investigations.
  
  
  RESULTS
  Here, we demonstrate for the first time that overexpression of Cav-1 in human lung cancer H23 cells significantly increased the formation of lamellipodia, whereas the suppression of Cav-1 using shRNA transfection had the opposite effect. Consistent with an increase in lamellipodia, Cav-1 overexpressing cells exhibited increased migratory activity in comparison to their parental, control-transfected, H23 cells. The induction of lamellipodia was demonstrated to occur via the Akt pathway because the addition of the Akt inhibitor LY294002 inhibited lamellipodia in both Cav-1-overexpressing and H23 cells. Additionally, transient transfection with Akt-siRNA significantly inhibited the formation of lamellipodia and the migration of Cav-1-overexpressing H23 cells. In addition, Cav-1 levels and the migratory action of other lung cancer cells, namely, H460 and A549, were assessed, and the migration of these cells was found to be correlated with the basal Cav-1 level.
  
  
  CONCLUSIONS
  These data showed that Cav-1 enhances cancer cell migration through Akt-mediated lamellipodia formation. Our results provide novel insights regarding the molecular mechanism controlling cancer cell migration, leading to a better understanding of cancer cell biology.
authors: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences and Cell-based Drug and Health Product Development Research Unit, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors: Pithi
authors: P
authors: Chanvorachote
authors: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences and Cell-based Drug and Health Product Development Research Unit, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors: Preedakorn
authors: P
authors: Chunhacha
authors: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences and Cell-based Drug and Health Product Development Research Unit, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
authors: Varisa
authors: V
authors: Pongrakhananon
keywords: Cancer migration; Caveolin-1; Lamellipodia; Lung cancer