title: C-terminal tensin-like gene functions as an oncogene and promotes cell motility in pancreatic cancer.
abstract: OBJECTIVE
  C-terminal tensin-like gene (CTEN, also known as TNS4) localizes to focal adhesions and is reported to function as an oncogene in colonic, breast, lung, and gastric cancers. Its role in pancreatic cancer is unknown and was thus investigated in this study.
  
  
  METHODS
  C-terminal tensinlike gene expression was evaluated by immunohistochemistry in a series of pancreatic cancers. Functional activity of the CTEN was tested by manipulating cellular CTEN levels using a dual approach of gene knockdown/forced expression.
  
  
  RESULTS
  The CTEN is overexpressed in 31 (70.45%) of 44 pancreatic cancers. Functionally, changes in CTEN level did not alter cellular proliferation, but CTEN levels were positively associated with enhanced colony-forming efficiency in both Panc-1 and PSN-1 cell lines. Forced CTEN expression in Panc-1 cells stimulated cell motility, whereas knockdown of CTEN in PSN-1 inhibited cell motility in both transwell migration and wound-healing assays. Evaluation of downstream targets demonstrated that alterations in CTEN levels induced changes in focal adhesion kinase and E-cadherin, whereas integrin-linked kinase (ILK) remained unchanged.
  
  
  CONCLUSIONS
  These are the first data showing an oncogenic role for CTEN in pancreatic cancer through promotion of colony formation and cell motility. The latter may be mediated by signaling through focal adhesion kinase and inhibiting E-cadherin.
authors: Division of Pathology, School of Molecular Medical Sciences, Queen's Medical Centre, Nottingham University, Nottingham, UK.
authors: Saleh
authors: S
authors: Al-Ghamdi
authors: Julien
authors: J
authors: Cachat
authors: Abdulkader
authors: A
authors: Albasri
authors: Mohammed
authors: M
authors: Ahmed
authors: Darryl
authors: D
authors: Jackson
authors: Abed
authors: A
authors: Zaitoun
authors: Naomi
authors: N
authors: Guppy
authors: William R
authors: WR
authors: Otto
authors: Malcolm R
authors: MR
authors: Alison
authors: Karin B
authors: KB
authors: Kindle
authors: Mohammad
authors: M
authors: Ilyas
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D000070876:Tensins; D013997:Time Factors; D046888:Tissue Array Analysis; D014162:Transfection; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D051417:Focal Adhesion Kinase 1; D008840:Microfilament Proteins; D015513:Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D000070876:Tensins; D000099200:Scaffold Protein ILK; C513384:CDH1 protein, human; C000603371:TNS4 protein, human; C496050:PTK2 protein, human