Integrin-linked kinase activity modulates the pro-metastatic behavior of ovarian cancer cells

// Lana Bruney 1, 2 , Yueying Liu 2, 3 , Anne Grisoli 2 , Matthew J. Ravosa 4 , M. Sharon Stack 1, 2, 3 1 Department of Medical Physiology & Pharmacology, University of Missouri School of Medicine, Columbia, MO, USA 2 Harper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA 3 Departments of Chemistry & Biochemistry and University of Notre Dame, Notre Dame, IN, USA 4 Biological Sciences, University of Notre Dame, Notre Dame, IN, USA Correspondence to: M. Sharon Stack, e-mail: sstack@nd.edu Keywords: integrin linked kinase, ovarian cancer, integrin, membrane type 1 matrix metalloproteinase, metastasis Received: January 07, 2016 Accepted: February 20, 2016 Published: March 03, 2016 ABSTRACT 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.