Year: 2006
Type: article
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 alphaVbeta3 integrin heterodimer, we determined that down-regulating uPAR subsequently causes the down-regulation of the alphaVbeta3 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.
DOI: 10.3892/ijo.28.3.633
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
Awards: G1320390427, Suppression of glioma invasion by a bicistronic constuct, G3760626908, G4091456469, G4366939855, Role of TFPI-2 in human gliomas invasiveness, Role of uPA and uPAR in Human Glioma Invasiveness, G4770781718, Inhibition of glioma tumor growth by antisense MMP-9, Cath B and uPAR si RNA constructs regressed glioma growth
OpenAlex ID: W2062012295