Caveolin-1 Promotes Autoregulatory, Akt-Mediated Induction of Cancer-Promoting Growth Factors in Prostate Cancer Cells

Caveolin-1 (cav-1) and the cancer-promoting growth factors vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF-beta 1), and fibroblast growth factor 2 (FGF2) are often found to be upregulated in advanced prostate cancer and other malignancies. However, the relationship between cav-1 overexpression and growth factor upregulation remains unclear. This report presents, to our knowledge, the first evidence that in prostate cancer cells, a positive autoregulatory feedback loop is established in which VEGF, TGF-beta 1, and FGF2 upregulate cav-1, and cav-1 expression, in turn, leads to increased levels of VEGF, TGF-beta 1, and FGF2 mRNA and protein, resulting in enhanced invasive activities of prostate cancer cells, i.e., migration and motility. Our results further show that cav-1-enhanced mRNA stability is a major mechanism underlying the upregulation of these cancer-promoting growth factors, and that PI3-K-Akt signaling is required for forming this positive autoregulatory feedback loop. (Mol Cancer Res 2009;7(11): 1781-91)