Document Detail


The PTEN phosphatase controls intestinal epithelial cell polarity and barrier function: role in colorectal cancer progression.
MedLine Citation:
PMID:  21203412     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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:
Marie-Josée Langlois; Sébastien Bergeron; Gérald Bernatchez; François Boudreau; Caroline Saucier; Nathalie Perreault; Julie C Carrier; Nathalie Rivard
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-23
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-07-05     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e15742     Citation Subset:  IM    
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.
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MeSH Terms
Descriptor/Qualifier:
Animals
Caco-2 Cells
Cell Line, Tumor
Cell Polarity
Colorectal Neoplasms / enzymology*
Epithelial Cells / cytology*
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Intestines / enzymology*
Mice
Mice, Nude
Mice, SCID
PTEN Phosphohydrolase / metabolism*
Grant Support
ID/Acronym/Agency:
CTP-82942//Canadian Institutes of Health Research; MT-14405//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
EC 3.1.3.67/PTEN Phosphohydrolase
Comments/Corrections

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