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PMID: 9501226 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 6 ·1998-03-17 ·Pages 3122-7

Efstathiou JA, Noda M, Rowan A, Dixon C, Chinery R, Jawhari A, Hattori T, Wright NA, Bodmer WF, Pignatelli M

Abstract

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.

MeSH Terms
Adenomatous Polyposis Coli Protein Apoptosis Cadherins/genetics,metabolism Carcinoma/metabolism Cell Adhesion Cell Compartmentation Colonic Neoplasms/metabolism Cytoskeletal Proteins/genetics,metabolism Desmoplakins Gene Expression Regulation, Neoplastic Growth Substances/genetics,metabolism Humans Mucins Muscle Proteins Neoplasm Proteins/genetics,metabolism Neuropeptides Nitriles/metabolism Peptides/genetics,metabolism Protein Binding Recombinant Proteins/metabolism Trans-Activators Trefoil Factor-2 Trefoil Factor-3 Tumor Cells, Cultured Tyrphostins alpha Catenin beta Catenin
Chemicals
Adenomatous Polyposis Coli Protein CTNNA1 protein, human CTNNB1 protein, human Cadherins Cytoskeletal Proteins Desmoplakins Growth Substances Mucins Muscle Proteins Neoplasm Proteins Neuropeptides Nitriles Peptides Recombinant Proteins TFF3 protein, rat Trans-Activators Trefoil Factor-2 Trefoil Factor-3 Tyrphostins alpha Catenin beta Catenin tyrphostin 25
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Efstathiou J A
Division of Investigative Science, Imperial College of Science, Technology and Medicine, Hammersmith Campus, Du Cane Road, London W12 ONN, United Kingdom.
Noda M
Rowan A
Dixon C
Chinery R
Jawhari A
Hattori T
Wright N A
Bodmer W F
Pignatelli M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.6.3122
Published
1998-03-17
Pages
3122-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19705
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1073/pnas.95.6.3122 PMC Full Text View journal details
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