title: The PTEN phosphatase controls intestinal epithelial cell polarity and barrier function: role in colorectal cancer progression.
abstract: BACKGROUND
  The PTEN phosphatase acts on phosphatidylinositol 3,4,5-triphosphates resulting from phosphatidylinositol 3-kinase (PI3K) activation. PTEN expression has been shown to be decreased in colorectal cancer. Little is known however as to the specific cellular role of PTEN in human intestinal epithelial cells. The aim of this study was to investigate the role of PTEN in human colorectal cancer cells.
  
  
  RESULTS
  Caco-2/15, HCT116 and CT26 cells were infected with recombinant lentiviruses expressing a shRNA specifically designed to knock-down PTEN. The impact of PTEN downregulation was analyzed on cell polarization and differentiation, intercellular junction integrity (expression of cell-cell adhesion proteins, barrier function), migration (wound assay), invasion (matrigel-coated transwells) and on tumor and metastasis formation in mice. Electron microscopy analysis showed that lentiviral infection of PTEN shRNA significantly inhibited Caco-2/15 cell polarization, functional differentiation and brush border development. A strong reduction in claudin 1, 3, 4 and 8 was also observed as well as a decrease in transepithelial resistance. Loss of PTEN expression increased the spreading, migration and invasion capacities of colorectal cancer cells in vitro. PTEN downregulation also increased tumor size following subcutaneous injection of colorectal cancer cells in nude mice. Finally, loss of PTEN expression in HCT116 and CT26, but not in Caco-2/15, led to an increase in their metastatic potential following tail-vein injections in mice.
  
  
  CONCLUSIONS
  Altogether, these results indicate that PTEN controls cellular polarity, establishment of cell-cell junctions, paracellular permeability, migration and tumorigenic/metastatic potential of human colorectal cancer cells.
authors.affiliation: Département d'Anatomie et de Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Canadian Institutes of Health Research Team on Digestive Epithelium, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Langlois
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bergeron
authors.forename: Gérald
authors.initials: G
authors.lastname: Bernatchez
authors.forename: François
authors.initials: F
authors.lastname: Boudreau
authors.forename: Caroline
authors.initials: C
authors.lastname: Saucier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Perreault
authors.forename: Julie C
authors.initials: JC
authors.lastname: Carrier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rivard
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D016764:Cell Polarity; D015179:Colorectal Neoplasms / Q000201:enzymology*; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007422:Intestines / Q000201:enzymology*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D051059:PTEN Phosphohydrolase / Q000378:metabolism*
chemical_list: D051059:PTEN Phosphohydrolase