Down-regulation of uPAR and Cathepsin B retards cofilin dephosphorylation

  • Authors:
    • Christopher S. Gondi
    • Neelima Kandhukuri
    • Shakuntala Kondraganti
    • Meena Gujrati
    • William C. Olivero
    • Dzung H. Dinh
    • Jasti S. Rao
  • View Affiliations

  • Published online on: March 1, 2006     https://doi.org/10.3892/ijo.28.3.633
  • Pages: 633-639
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Abstract

Cathepsin B and uPAR play key roles in cancer cell migration and invasion. Here, we demonstrate that the simultaneous, siRNA-mediated down-regulation of uPAR and cathepsin B inhibits glioma cell migration and is accompanied by cytoskeletal condensation. We show that the dephosphorylation of cofilin is inhibited by the down-regulation of uPAR alone and, to a lesser extent, by the down-regulation of cathepsin B alone, and that the effect was much higher with the down-regulation of both molecules by pUC. Using FACS analysis and western blotting for the αVβ3 integrin heterodimer, we determined that down-regulating uPAR subsequently causes the down-regulation of the αVβ3 integrin heterodimer. As evidenced by western blot analysis of ERK1/2, pERK1/2, p38MAPK, p-p38MAPK, AKT, pAKT and PI3-k, the MEK and PI3-k pathways are inhibited. From cytoskeleton studies, we observed that the down-regulation of uPAR caused cytoskeletal condensation and that the simultaneous down-regulation of uPAR and cathepsin B was even more effective at inducing cytoskeletal condensation than uPAR alone. Our results demonstrate the relevance of uPAR in cytoskeletal dynamics and the potential of uPAR and cathepsin B as targets in the treatment of malignant gliomas.

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March 2006
Volume 28 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Gondi CS, Kandhukuri N, Kondraganti S, Gujrati M, Olivero WC, Dinh DH and Rao JS: Down-regulation of uPAR and Cathepsin B retards cofilin dephosphorylation. Int J Oncol 28: 633-639, 2006
APA
Gondi, C.S., Kandhukuri, N., Kondraganti, S., Gujrati, M., Olivero, W.C., Dinh, D.H., & Rao, J.S. (2006). Down-regulation of uPAR and Cathepsin B retards cofilin dephosphorylation. International Journal of Oncology, 28, 633-639. https://doi.org/10.3892/ijo.28.3.633
MLA
Gondi, C. S., Kandhukuri, N., Kondraganti, S., Gujrati, M., Olivero, W. C., Dinh, D. H., Rao, J. S."Down-regulation of uPAR and Cathepsin B retards cofilin dephosphorylation". International Journal of Oncology 28.3 (2006): 633-639.
Chicago
Gondi, C. S., Kandhukuri, N., Kondraganti, S., Gujrati, M., Olivero, W. C., Dinh, D. H., Rao, J. S."Down-regulation of uPAR and Cathepsin B retards cofilin dephosphorylation". International Journal of Oncology 28, no. 3 (2006): 633-639. https://doi.org/10.3892/ijo.28.3.633