Molecular mechanisms involved in TFF3 peptide-mediated modulation of the E-cadherin/catenin cell adhesion complex.
TFF3 is a member of the TFF-domain peptide family which is constitutively expressed in mucous epithelial tissues where it acts as a motogenic factor and plays an important role during epithelial restitution after wounding and during inflammation. In contrast to these beneficial functions, TFFs were also reported to be involved in cell scattering and tumor invasion. These changes in epithelial cell morphology and motility are associated with a modulation of cell contacts. In this respect, we here investigated the E-cadherin/catenin cell adhesion complex in FLAG-hTFF3-transfected HT29/B6 and MDCK cells. In hTFF3-transfected cells the amount of E-cadherin is reduced with a concomitant reduction of alpha- and beta-catenin levels. On one hand, E-cadherin expression is lowered at the transcriptional level as shown by multiplex RT-PCR analysis. This decrease does not depend on differences in the promoter methylation status as shown by methylation-specific PCR. On the other hand, pulse-chase experiments showed a reduction in the E-cadherin half-life in hTFF3-transfected cells reflecting increased E-cadherin degradation. In summary, hTFF3 induces transcriptional and posttranslational processes resulting in a modulation of E-cadherin-mediated cell-cell contacts that may play an important role in the paradoxical benefical and pathogenic function of TFF peptides.
Meyer zum Büschenfelde
Dirk
D
Institut für Klinische Chemie und Pathobiochemie, Charité-Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Hoschützky
Heinz
H
Tauber
Rudolf
R
Huber
Otmar
O
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D008745:Methylation; D009077:Mucins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D010455:Peptides; D011401:Promoter Regions, Genetic / Q000235:genetics; D011489:Protein Denaturation / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D000071163:Trefoil Factor-1; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D011506:Proteins; C051838:TFF1 protein, human; C082495:TFF3 protein, human; D015534:Trans-Activators; D000071163:Trefoil Factor-1; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; D051176:beta Catenin