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 journalArticle

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 α V β 3 integrin heterodimer, we determined that down-regulating uPAR subsequently causes the down-regulation of the α V β 3 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
Volume28
Issue number3
StatePublished - Mar 1 2006

Fingerprint

Actin Depolymerizing Factors
Cathepsin B
Down-Regulation
Integrins
Glioma
Cell Movement
Western Blotting
Mitogen-Activated Protein Kinase Kinases
Cytoskeleton
Small Interfering RNA

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gondi, C. S., Neelima, K., Shakuntala, K., 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(3), 633-639.

Down-regulation of uPAR and cathepsin B retards cofilin dephosphorylation. / Gondi, Christopher S.; Neelima, Kandhukuri; Shakuntala, Kondraganti; Gujrati, Meena; Olivero, William C.; Dinh, Dzung H.; Rao, Jasti S.

In: International journal of oncology, Vol. 28, No. 3, 01.03.2006, p. 633-639.

Research output: Contribution to journalArticle

Gondi, CS, Neelima, K, Shakuntala, K, Gujrati, M, Olivero, WC, Dinh, DH & Rao, JS 2006, 'Down-regulation of uPAR and cathepsin B retards cofilin dephosphorylation', International journal of oncology, vol. 28, no. 3, pp. 633-639.
Gondi CS, Neelima K, Shakuntala K, Gujrati M, Olivero WC, Dinh DH et al. Down-regulation of uPAR and cathepsin B retards cofilin dephosphorylation. International journal of oncology. 2006 Mar 1;28(3):633-639.
Gondi, Christopher S. ; Neelima, Kandhukuri ; Shakuntala, Kondraganti ; Gujrati, Meena ; Olivero, William C. ; Dinh, Dzung H. ; Rao, Jasti S. / Down-regulation of uPAR and cathepsin B retards cofilin dephosphorylation. In: International journal of oncology. 2006 ; Vol. 28, No. 3. pp. 633-639.
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