Integrin-Linked Kinase Activity Modulates the Pro-Metastatic Behavior of Ovarian Cancer Cells.

Epithelial ovarian cancer (EOC) is the most fatal gynecologic cancer in the U.S.,resulting in >14,000 deaths/year. Most women are diagnosed at late stage with widely disseminated intra-peritoneal metastatic disease,resulting in a 5-year survival rate of <30%. EOCs spread via direct extension and exfoliation into the peritoneal cavity,adhesion to peritoneal mesothelial cells,mesothelial cell retraction to expose sub-mseothelial matrix and anchoring in the type I collagen-rich matrix to generate secondary lesions. As a molecular-level understanding of EOC metastasis may identify novel therapeutic targets,the current study evaluated the expression and activity of integrin-linked kinase (ILK),a Ser/Thr protein kinase activated upon integrin-mediated adhesion. Results show that ILK is co-expressed in EOC with the pro-metastatic enzyme membrane type 1 matrix metalloproteinase (MT1-MMP) and catalyzed phosphorylation of the cytoplasmic tail of the proteinase. Downregulation of ILK expression or activity reduced adhesion to and invasion of collagen gels and organotypic meso-mimetic cultures. As an initial early event in EOC metastasis is integrin-mediated adhesion,these results suggest that further evaluation of ILK inhibitors as anti-metastatic agents in EOC is warranted.