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Caveolin-1 regulates VEGF-stimulated angiogenic activities in prostate cancer and endothelial cells
| Content Provider | Scilit |
|---|---|
| Author | Tahir, Salahaldin A. Park, Sanghee Thompson, Timothy C. |
| Copyright Year | 2009 |
| Description | Journal: Cancer Biology & Therapy Caveolin-1 (cav-1) is a multifunctional protein and major component of caveolae membranes serving important functions related to signal transduction, endocytosis, transcytosis, and molecular transport. We previously showed that cav-1 is overexpressed and secreted by metastatic prostate cancer cells. We now report that cav-1 gene transduction (Adcav-1) or recombinant cav-1 (rcav-1) protein treatment of cav-1-negative prostate cancer cell line LP-LNCaP or cav-1 -/- endothelial cells potentiated VEGF-stimulated angiogenic signaling. Down-regulation of cav-1 in prostate cancer cell line PC-3 or human umbilical vein endothelial cells (HUVECs) through cav-1 siRNA significantly reduced basal and VEGFstimulated phosphorylation of VEGFR2 (Y951), PLCγ1 (Y783) and/or Akt (S473 & T308) relative to those in control siRNA treated cells. Additionally rcav-1 stimulation of cav-1 siRNA treated HUVECs restored this signaling pathway. Confocal microscopy and immunoprecipitation analysis revealed association and colocalization of VEGFR2 and PLCγ1 with cav-1 following VEGF stimulation in HUVECs. Interestingly, treatment of HUVECs with cav-1 scaffolding domain (CSD) caused significant reduction in the VEGF-stimulated phosphorylation of VEGFR2, PLCγ1 and Akt suggesting that CSD inhibits cav-1-mediated angiogenic signaling. VEGF stimulation of HUVECs significantly increased tubule length and cell migration, but this stimulatory effect was significantly reduced by cav-1 siRNA and/or CSD treatment. The present study demonstrates that cav-1 regulates VEGF-stimulated VEGFR2 autophosphorylation and activation of downstream angiogenic signaling, possibly through compartmentalization of specific signaling molecules. Our results provide mechanistic insight into the role of cav-1 in prostate cancer and suggest the use of CSD as a therapeutic tool to suppress angiogenic signaling in prostate cancer. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/cbt.8.23.10138?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887683/pdf |
| Ending Page | 2294 |
| Page Count | 11 |
| Starting Page | 2284 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/cbt.8.23.10138 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 23 |
| Volume Number | 8 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2009-12-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Biology & Therapy Cell Biology Caveolin-1 Scaffolding Domain Angiogenesis |
| Content Type | Text |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
