Abstract
Caveolin-1 (cav-1) and the cancer-promoting growth factors vascular endothelial growth factor (VEGF), transforming growth factor beta1 (TGF-beta1), 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-beta1, and FGF2 upregulate cav-1, and cav-1 expression, in turn, leads to increased levels of VEGF, TGF-beta1, 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Blotting, Western
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Caveolin 1 / biosynthesis*
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Caveolin 1 / genetics
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Caveolin 1 / metabolism
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Cell Movement / physiology
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Disease Progression
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Enzyme Activation
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Fibroblast Growth Factor 2 / biosynthesis
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / metabolism
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Homeostasis
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Humans
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Intercellular Signaling Peptides and Proteins / biosynthesis*
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Intercellular Signaling Peptides and Proteins / genetics
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Male
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Mice
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Oncogene Protein v-akt / metabolism*
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology
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RNA Stability
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Signal Transduction
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Transforming Growth Factor beta1 / biosynthesis
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / metabolism
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Up-Regulation
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Vascular Endothelial Growth Factor A / biosynthesis
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Caveolin 1
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Intercellular Signaling Peptides and Proteins
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Transforming Growth Factor beta1
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Vascular Endothelial Growth Factor A
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Fibroblast Growth Factor 2
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Oncogene Protein v-akt