Reduction of protein kinase C ζ inhibits migration and invasion of human glioblastoma cells

Abstract

Glioblastomas are the most aggressive forms of primary brain tumors with their tendency to invade surrounding healthy brain tissues, rendering them largely incurable. In this report, we used small-interference RNA technology to knock down the expression of protein kinase C (PKC) ζ, which resulted in specific and massive impairment of glioblastoma cell migration and invasion. We also explained the fundamental molecular processes of glioblastoma migration and invasion in which PKCζ is a participant. The silence of PKCζ expression likewise impaired the phosphorylation of LIN-11, Isl1 and MEC-3 protein domain kinase (LIMK) and cofilin, which is a critical step in cofilin recycling and actin polymerization. Consistent with the defects in cell adhesion, phosphorylation of integrin β1 was also dampened. Therefore, PKCζ regulated both cytoskeleton rearrangement and cell adhesion, which contributed to cell migration. Additionally, there was down-regulation of matrix metalloprotease-9 expression in siPKCζ/LN-229 cells, which coincided with decreased invasion both in vitro and in vivo. These results indicate that PKCζ is involved in the control of glioblastoma cell migration and invasion by regulating the cytoskeleton rearrangement, cell adhesion, and matrix metalloprotease-9 expression. Collectively, these findings suggest that PKCζ is a potential therapeutic target for glioblastoma infiltration. © 2009 International Society for Neurochemistry.