title: C-terminal tensin-like protein mediates invasion of human lung cancer cells and is regulated by signal transducer and activator of transcription 3.
abstract: OBJECTIVE
  C-terminal tensin-like (Cten) protein, a component of focal adhesions, contributes to cell motility and invasion in multiple human cancers. Epidermal growth factor can activate signal transducer and activator of transcription 3, and both contribute to invasion through focal adhesion interactions. We hypothesize that Cten may mediate invasion of lung cancer cells provided by epidermal growth factor via signal transducer and activator of transcription 3.
  
  
  METHODS
  Four human non-small cell lung cancer cell lines were treated with epidermal growth factor to evaluate activation of the signal transducer and activator of transcription 3 pathway and induction of Cten expression. Chemical inhibition of signal transducer and activator of transcription 3 was used to evaluate the effect on epidermal growth factor-induced Cten expression. Protein expression was quantified by Western blot. H125 and A549 cells were transduced with short-hairpin RNA via lentiviral vector to knockdown expression of Cten. An in vitro transwell invasion assay was used to assess the effects of Cten knockdown on cell invasion (n = 3 for all experiments).
  
  
  RESULTS
  Stimulation of lung cancer cells with epidermal growth factor activated the signal transducer and activator of transcription 3 pathway and induced expression of Cten in all cell lines. Signal transducer and activator of transcription 3 inhibition significantly reduced epidermal growth factor-induced expression of Cten in H125 (P < .0001), H358 (P = .006), and H441 (P = .014) cells in a dose-dependent manner. Knockdown of Cten expression resulted in significant decreases in cellular invasion in both H125 (P = .0036) and A549 (P = .0006) cells.
  
  
  CONCLUSIONS
  These are the first findings in lung cancer to demonstrate that Cten expression mediates invasion of human lung cancer cells and is upregulated by epidermal growth factor via signal transducer and activator of transcription 3 pathway. Cten should be considered a potential therapeutic target for lung cancer.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver, School of Medicine, Aurora, Colo.
authors.forename: Daine T
authors.initials: DT
authors.lastname: Bennett
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver, School of Medicine, Aurora, Colo.
authors.forename: Thomas Brett
authors.initials: TB
authors.lastname: Reece
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver, School of Medicine, Aurora, Colo.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Foley
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver, School of Medicine, Aurora, Colo.
authors.forename: Ayla
authors.initials: A
authors.lastname: Sjoberg
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver, School of Medicine, Aurora, Colo.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver, School of Medicine, Aurora, Colo.
authors.forename: David A
authors.initials: DA
authors.lastname: Fullerton
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver, School of Medicine, Aurora, Colo. Electronic address: michael.weyant@ucdenver.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
mesh_terms: D000636:Aminosalicylic Acids / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D000070876:Tensins; D013997:Time Factors; D014162:Transfection
chemical_list: D000636:Aminosalicylic Acids; D001557:Benzenesulfonates; D008840:Microfilament Proteins; C520337:NSC 74859; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C000603371:TNS4 protein, human; D000070876:Tensins; D004815:Epidermal Growth Factor