Down-regulation of uPAR and cathepsin B retards cofilin dephosphorylation

Christopher S. Gondi, Kandhukuri Neelima, Kondraganti Shakuntala, Meena Gujrati, William C. Olivero, Dzung H. Dinh, Jasti S. Rao

Research output: Contribution to journalArticlepeer-review


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 downregulation 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.

Original languageEnglish (US)
Pages (from-to)633-639
Number of pages7
JournalInternational journal of oncology
Issue number3
StatePublished - Mar 2006
Externally publishedYes


  • Actin
  • Cathepsin B
  • Cofilin
  • Cytoskeleton
  • Integrin
  • uPAR

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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