Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.
Intestinal trefoil factor 3 (TFF3) is a member of the trefoil family of peptides, small molecules constitutively expressed in epithelial tissues, including the gastrointestinal tract. TFF3 has been shown to promote migration of intestinal epithelial cells in vitro and to enhance mucosal healing and epithelial restitution in vivo. In this study, we evaluated the effect of recombinant TFF3 (rTFF3) stimulation on the expression and cellular localization of the epithelial (E)-cadherin-catenin complex, a prime mediator of Ca2+ dependent cell-cell adhesion, and the adenomatous polyposis coli (APC)-catenin complex in HT29, HCT116, and SW480 colorectal carcinoma cell lines. Stimulation by rTFF3 (10(-9) M and 10(-8) M) for 20-24 hr led to cell detachment and to a reduction in intercellular adhesion in HT29 and HCT116 cells. In both cell lines, E-cadherin expression was down-regulated. The expression of APC, alpha-catenin and beta-catenin also was decreased in HT29 cells, with a translocation of APC into the nucleus. No change in either cell adhesion or in the expression of E-cadherin, the catenins, and APC was detected in SW480 cells. In addition, TFF3 induced DNA fragmentation and morphological changes characteristic of apoptosis in HT29. Tyrphostin, a competitive inhibitor of protein tyrosine kinases, inhibited the effects of TFF3. Our results indicate that by perturbing the complexes between E-cadherin, beta-catenin, and associated proteins, TFF3 may modulate epithelial cell adhesion, migration, and survival.
Efstathiou
J A
JA
Division of Investigative Science, Imperial College of Science, Technology and Medicine, Hammersmith Campus, Du Cane Road, London W12 ONN, United Kingdom.
Noda
M
M
Rowan
A
A
Dixon
C
C
Chinery
R
R
Jawhari
A
A
Hattori
T
T
Wright
N A
NA
Bodmer
W F
WF
Pignatelli
M
M
D025601:Adenomatous Polyposis Coli Protein; D017209:Apoptosis; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002448:Cell Adhesion; D002451:Cell Compartmentation; D003110:Colonic Neoplasms / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D051180:Desmoplakins; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009077:Mucins; D009124:Muscle Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides; D009570:Nitriles / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured; D020032:Tyrphostins; D051178:alpha Catenin; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D009479:Neuropeptides; D009570:Nitriles; D010455:Peptides; D011994:Recombinant Proteins; C099037:TFF3 protein, rat; D015534:Trans-Activators; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D020032:Tyrphostins; D051178:alpha Catenin; D051176:beta Catenin; C079836:tyrphostin 25