التفاصيل البيبلوغرافية
العنوان: |
Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells. |
المؤلفون: |
Cavallo-Medved, Dora1,2 dcavallo@med.wayne.edu, Jianxin Mai1, Dosescu, Julie1, Sameni, Mansoureh1, Sloane, Bonnie F.1,2 |
المصدر: |
Journal of Cell Science. 4/1/2005, Vol. 118 Issue 7, p1493-1503. 11p. 2 Color Photographs, 17 Graphs. |
مصطلحات موضوعية: |
*RECTAL cancer, *UROKINASE, *PLASMINOGEN activators, *CELL membranes, *CELL receptors, *ONCOLOGY |
مستخلص: |
Cathepsin B and pro-urokinase plasminogen activator (pro-uPA) localize to the caveolae of HCT 116 human colorectal carcinoma cells, an association mediated by active KRAS. In this study, we established a stable HCT 116 cell line with a gene encoding antisense caveolin-1 (AS-cav-1) to examine the effects of caveolin-1, the main structural protein of caveolae, on the expression and localization of cathepsin B and pro-uPA, and their cell-surface receptors p11 and uPA receptor (uPAR), respectively. AS-cav-1 HCT 116 cells secreted less procathepsin B than control (empty vector) cells as measured by immunoblotting and pepsin activation of the proenzyme. Expression and secretion of pro-uPA was also downregulated in AS-cav-1 HCT 116 cells. Localization of cathepsin B and pro-uPA to caveolae was reduced in AS-cav-1 HCT 116 cells, and these cells expressed less total and caveolae-associated p11 and UPAR compared with control cells. Previous studies have shown that uPAR forms a complex with caveolin-1 and β1-integrin, and we here show that downregulation of caveolin-1 also suppressed the localization of β1-integrin to caveolae of these cells. Finally, downregulation of caveolin-1 in HCT 116 cells inhibited degradation of the extracellular matrix protein collagen IV and the invasion of these cells through Matrigel. Based on these results, we hypothesize that caveolin-1 affects the expression and localization of cathepsin B and pro-uPA, and their receptors, thereby mediating cell-surface proteolytic events associated with invasion of colon cancer cells. [ABSTRACT FROM AUTHOR] |
قاعدة البيانات: |
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