Abstract
BackgroundThe enhancement of migration is critical for facilitating cancer cell metastasis.MethodLung 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.ResultsHere, 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.ConclusionThese 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.
Highlights
The enhancement of migration is critical for facilitating cancer cell metastasis
Caveolin-1 enhances lamellipodia formation and migration in non-small cell lung cancer H23 cells To test the effect of Cav-1 protein in the regulation of lamellipodia formation, we stably transfected H23 cells with Cav-1-overexpression, control, shRNA-Cav1 or shCtrl plasmids and selected stable transfectants using an appropriate protocol
These results demonstrate for the first time that Cav-1 plays a positive role in the formation of cellular lamellipodia in lung cancer cells
Summary
The enhancement of migration is critical for facilitating cancer cell metastasis. Understanding the molecular mechanisms that control cancer cell behavior is important for the development of novel anti-cancer strategies. An enhanced migration ability of the cells is among the key factors facilitating metastasis, a major cause of death in this type of cancer. Lamellipodia are widely accepted to be critical for directional migration in many cells [1]. Cell migration is initiated by the formation of pseudopodia such as lamellipodia, sheet-like cellular protrusions that are enriched with F-actin. The formation of lamellipodia involves multi-step processes of actin polymerization and depolymerization [3]; actin filaments are arranged into a sheet-like network of lamellipodia at the leading edge of the cells during movement [3]. The defined molecular pathways controlling the formation of lamellipodia have been elusive to date, and such insight is considerably vital to the discovery of novel molecular targets in the development of antimetastasis therapies
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