title: Integrin-linked kinase activity modulates the pro-metastatic behavior of ovarian cancer cells.
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.
authors.affiliation: Department of Medical Physiology & Pharmacology, University of Missouri School of Medicine, Columbia, MO, USA.|Harper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.
authors.forename: Lana
authors.initials: L
authors.lastname: Bruney
authors.affiliation: Harper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.|Departments of Chemistry & Biochemistry and University of Notre Dame, Notre Dame, IN, USA.
authors.forename: Yueying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Harper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Grisoli
authors.affiliation: Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ravosa
authors.affiliation: Department of Medical Physiology & Pharmacology, University of Missouri School of Medicine, Columbia, MO, USA.|Harper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.|Departments of Chemistry & Biochemistry and University of Notre Dame, Notre Dame, IN, USA.
authors.forename: M Sharon
authors.initials: MS
authors.lastname: Stack
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D053511:Matrix Metalloproteinase 14; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C507086:MMP14 protein, human
keywords: integrin; integrin linked kinase; membrane type 1 matrix metalloproteinase; metastasis; ovarian cancer