Repressed E-cadherin expression in the lower crypt of human small intestine: a cell marker of functional relevance.
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.
Escaffit
Fabrice
F
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.
Perreault
Nathalie
N
Jean
Dominique
D
Francoeur
Caroline
C
Herring
Elizabeth
E
Rancourt
Claudine
C
Rivard
Nathalie
N
Vachon
Pierre H
PH
Paré
Frédéric
F
Boucher
Marie-Pierre
MP
Auclair
Joëlle
J
Beaulieu
Jean-François
JF
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
D015415:Biomarkers; C495270:CTNNB1 protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin