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Mutated epithelial cadherin is associated with increased tumorigenicity and loss of adhesion and of responsiveness to the motogenic trefoil factor 2 in colon carcinoma cells
Citation
Efstathiou, JA and Liu, D and Wheeler, JMD and Kim, HC and Beck, NE and Ilyas, M and Karayiannakis, AJ and Mortensen, NJM and Kmiot, W and Playford, RJ and Pignatelli, M and Bodmer, WF, Mutated epithelial cadherin is associated with increased tumorigenicity and loss of adhesion and of responsiveness to the motogenic trefoil factor 2 in colon carcinoma cells, National Academy of Sciences of The United States of America. Proceedings, 96, (5) pp. 2316-2321. ISSN 0027-8424 (1998) [Refereed Article]
DOI: doi:10.1073/pnas.96.5.2316
Abstract
Epithelial (E)-cadherin and its associated cytoplasmic proteins (α-, β-, and γ-catenins) are important mediators of epithelial cell-cell adhesion and intracellular signaling. Much evidence exists suggesting a tumor/invasion suppressor role for E-cadherin, and loss of expression, as well as mutations, has been described in a number of epithelial cancers. To investigate whether E-cadherin gene (CDH1) mutations occur in colorectal cancer, we screened 49 human colon carcinoma cell lines from 43 patients by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. In addition to silent changes, polymorphisms, and intronic variants in a number of the cell lines, we detected frameshift single-base deletions in repeat regions of exon 3 (codons 120 and 126) causing premature truncations at codon 216 in four replication-error-positive (RER+) cell lines (LS174T, HCT116, GP2d, and GP5d) derived from 3 patients. In LS174T such a mutation inevitably contributes to its lack of E-cadherin protein expression and function. Transfection of full-length E-cadherin cDNA into LS174T cells enhanced intercellular adhesion, induced differentiation, retarded proliferation, inhibited tumorigenicity, and restored responsiveness to the migratory effects induced by the motogenic trefoil factor 2 (human spasmolytic polypeptide). These results indicate that, although inactivating E-cadherin mutations occur relatively infrequently in colorectal cancer cell lines overall (3/43 = 7%), they are more common in cells with an RER+ phenotype (3/10 = 30%) and may contribute to the dysfunction of the E- cadherin-catenin-mediated adhesion/signaling system commonly seen in these tumors. These results also indicate that normal E-cadherin-mediated cell adhesion can restore the ability of colonic tumor cells to respond to trefoil factor 2.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Clinical sciences |
| Research Field: | Gastroenterology and hepatology |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Playford, RJ (Professor Ray Playford) |
| ID Code: | 72868 |
| Year Published: | 1998 |
| Web of Science® Times Cited: | 99 |
| Deposited By: | Research Division |
| Deposited On: | 2011-09-02 |
| Last Modified: | 2011-09-05 |
| Downloads: | 0 |
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