title: Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target.
abstract: BACKGROUND
  Integrin-linked kinase (ILK) is a serine-threonine kinase that regulates interactions between the cell and the extracellular matrix. In many cancers, overexpression of ILK leads to increased cell proliferation, motility, and invasion. We hypothesized that ILK functions as a regulator of viability and migration in thyroid cancer cells.
  
  
  METHODS
  Eleven human thyroid cancer cell lines were screened for ILK protein expression. The cell lines with the greatest expression were treated with either ILK small interfering RNA (siRNA) or a novel ILK inhibitor, T315, and the effects were evaluated via Western blot and migration assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays were performed to assess cell viability.
  
  
  RESULTS
  siRNA against ILK decreased phosphorylation of downstream effectors Akt and MLC, as well as decreased migration. Treatment with T315 showed a dose-related decrease in both Akt and MLC phosphorylation, as well as decreased migration. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays showed T315 to have an half maximal inhibitory concentration of less than 1 μM in cell lines with high ILK expression.
  
  
  CONCLUSIONS
  ILK is expressed differentially in thyroid cancer cell lines. Both ILK siRNA and T315 inhibit motility of thyroid cancer cell lines, and T315 is shown to be cytotoxic at low concentrations. Altogether, our study suggests that ILK may represent an important kinase in aggressive thyroid cancers.
authors.affiliation: Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address: lawrence.shirley@osumc.edu.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Shirley
authors.affiliation: Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: Samantha
authors.initials: S
authors.lastname: McCarty
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH.
authors.forename: Ming-Chen
authors.initials: MC
authors.lastname: Yang
authors.affiliation: Division of Endocrinology, The Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Saji
authors.affiliation: Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: John
authors.initials: J
authors.lastname: Phay
authors.affiliation: Division of Endocrinology, The Ohio State University Wexner Medical Center, Columbus, OH.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Ringel
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH.
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology*; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D000099200:Scaffold Protein ILK
chemical_list: D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK