The migratory activity of cancer cells is generally recognized as an important factor for successful metastasis. In lung cancer, the high mortality rate is caused by cancer metastasis, which in this type of cancer is frequently found at the time of diagnosis [
13]. Cancer researchers have paid much attention to identifying possible strategies for inhibiting cancer migration, and knowledge of the molecular basis of such cell activity is highly critical.
Cav-1 is a major protein component of the cell structures called caveolae. This protein has lately garnered a significant amount of attention in cancer research because a large number of studies have indicated its role in potentiating cancer cells in many ways [
14‐
16]. Recently, we reported a role for Cav-1 in the regulation of anoikis [
4‐
6], migration and invasion [
7] in a lung cancer cell model; however, its role in controlling lamellipodia is still unknown. The migration of cancer cells involves several regulatory proteins, and among them Akt plays a central role. An increase in cellular activated Akt is observed in metastatic tumors, and activated Akt has been shown to increase cell motility [
17,
18]. Akt contributes to the polymerization of actin protein, resulting in the cell protrusions called lamellipodia. Here, we reveal for the first time that Cav-1 has a function in controlling the lamellipodia formation that leads to cell migration. The number of lamellipodia per cell has been correlated with an increased migratory behavior of cancer cells [
2,
19,
20]. Our results are consistent, as we found that both lamellipodia and migration significantly increased in Cav-1-overexpressing cells (Figures
1 and
2). Additionally, shRNA transfection confirmed this function of Cav-1 by causing the opposite effect.To provide a molecular mechanism by which Cav-1 regulates lamellipodia, an Akt inhibitor as well as siRNA-Akt were used. We found that the decrease in activated Akt caused by the Akt inhibitor or siRNA transfection was able to abolish the effect of Cav-1 (Figures
3 and
4), suggesting that Cav-1 up-regulates lamellipodia via an Akt-dependent mechanism. Because the up-regulation Cav-1 was demonstrated in tumor tissues from patients and the high expression level of this protein was linked to a poor prognosis, we hypothesized that the basal expression level of Cav-1 protein may affect the migratory activity of lung cancer cells. Human lung cancer cells, including H460 and A549 cells, were subjected to a western blot analysis, and our results showed that the cells possessing a higher level of Cav-1 exhibited greater motility (Figure
5). These observations support the results of our experiments that an increase in cellular Cav-1 contributes to an increase in cell motility. Although the migration activity of lung cancer cells is likely to involve several pathways, our results and observations indicate that Cav-1, at least in part, plays a critical role in the regulation of lung cancer cell migration.
In conclusion, the present study reveals information regarding an endogenous protein that plays a significant role in cancer cell behavior. This insight may provide a better understanding of lung cancer and lead to the development of novel therapies.