行政院國家科學委員會專題研究計畫成果報告:caveolin-1增強肺腺癌轉移能力之細胞生物暨分子機制之探究(2/2)

Caveolin-1 is a 21-24 kDa transmembrane protein and functions as a fundamental scaffold for caveolae. During transformation of many epithelial cells including lung, breast, prostate, and renal cancers, loss of caveolin-1 expression is necessary. Paradoxically, re-expression of caveolin-1 correlates positively with tumor cell invasiveness seen in prostate, breast, and lung adenocarcinoma. We have reported that the metastasis ability is positively correlated with filopodia formation induced by caveolin-1 in CL-cells. Furthermore, the targeting of caveolin-1 into cytoplasmic lipid droplets and plasma membrane is necessary for promoting both filopodia formation and celluar invasiveness of CL- cells. In this report, we described growth inhibition conferred by caveolin-1 in human lung adenocarcinoma cell lines. Such caveolin-1 induced growth inhibition in CL-cells is not mediated through the effect in cell cycle progression. The different invasive ability of CL-cells is not attributed to differential pools of caveolin-1-interacting molecules as revealed by analysis of immunoprecipitate pulled down by TAP-caveolin-1 fusion protein. Moreover, we have shown that both α− and β- form of caveolin-1 could mediate lung adenocarcinoma invasiveness and that the scaffolding and membrane insertion domain of caveolin-1 were required for tumor invasiveness. We also showed that gelsolin, an actin anticapping protein, colocalized with caveolin-1 in CL- cells. These results prompt us a hypothesized model that caveolin-1 might negatively regulate gelsolin and promote the transition of filopodia from lamellipodia