Protein kinase Cδ signaling downstream of the EGF receptor mediates migration and invasiveness of prostate cancer cells

Tumor progression to the invasive phenotype occurs secondary to upregulated signaling from growth factor receptors that drive key cellular responses like proliferation.. migration, and invasion. We hypothesized that Protein kinase C delta (PKC delta)-mediated transcellular contractility is required for migration and invasion of prostate tumor cells. Two invasive human prostate cancer cell lines, DU145 cells overexpressing wildtype human EGFR (DU145WT) and PC3 cells, were studied. PKC delta is overexpressed in these cells relative to normal prostate epithelial cells, and is activated downstream of EGFR leading to cell motility via modulation of myosin light chain activity. Abrogation of PKC delta using Rottlerin and specific siRNA significantly decreased migration and invasion of both cell lines in vitro. Both PKC delta and phosphorylated PKC delta protein levels were higher in human prostate cancer tissue relative to normal donor prostate as assessed by Western blotting and immunohistochemistry. Thus, we conclude that PKC delta inhibition can limit migration and invasion of prostate cancer cells. (c) 2006 Elsevier Inc. All rights reserved.