title: Repressed E-cadherin expression in the lower crypt of human small intestine: a cell marker of functional relevance.
abstract: In epithelia, abnormal expression of E-cadherin is related to pathologies involving a loss of cell polarization and/or differentiation. However, recent observations suggest that E-cadherin could also be repressed under physiological conditions, such as in some epithelial stem cell lineages. In the present work, we have analyzed E-cadherin expression in human intestinal epithelial cell progenitors and investigated its potential role. E-cadherin expression was analyzed along the crypt-villus axis by immunofluorescence on cryosections of small intestine. E-cadherin was found to be differentially expressed, being significantly weaker in the cells located at the bottom of the crypts. Surprisingly, neither the E-cadherin protein nor transcript were detected in a normal human intestinal epithelial (HIEC) crypt cell model isolated in our laboratory, whereas other E-cadherin-related components such as catenins and APC were present. Forced expression of E-cadherin in HIEC cells increased membrane-associated beta-catenin and was accompanied by the appearance of junction-like structures at the cell-cell interface. Functionally, cell kinetics and p21Cip levels were found to be altered in the E-cadherin expressing HIEC cells as compared to controls. Furthermore, a significant reduction of the migration abilities and an increase in sensitivity to anoikis were also observed. These results suggest that down-regulated expression of E-cadherin is a human intestinal crypt base cell-related feature that appears to be of functional relevance for the maintenance of the progenitor cell population.
authors.affiliation: Département d'anatomie et de Biologie Cellulaire, Faculté de médecine, Université de Sherbrooke, CIHR Group in Functional Development and Physiopathology of the Digestive Tract, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Escaffit
authors.forename: Nathalie
authors.initials: N
authors.lastname: Perreault
authors.forename: Dominique
authors.initials: D
authors.lastname: Jean
authors.forename: Caroline
authors.initials: C
authors.lastname: Francoeur
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Herring
authors.forename: Claudine
authors.initials: C
authors.lastname: Rancourt
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rivard
authors.forename: Pierre H
authors.initials: PH
authors.lastname: Vachon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Paré
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Boucher
authors.forename: Joëlle
authors.initials: J
authors.lastname: Auclair
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Beaulieu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D023102:Anoikis; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D017491:Genes, APC; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology*; D007700:Kinetics; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
chemical_list: D015415:Biomarkers; C495270:CTNNB1 protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin