Loss of E-cadherin expression or function in tumors leads to a more invasive phenotype. In this study, we investigated whether the invasion suppressor activity of E-cadherin is mediated directly by tighter physical cell adhesion, indirectly by sequestering β-catenin and thus antagonizing β-catenin/T cell factor (TCF) signaling, or by other signaling pathways. To distinguish mechanisms, we expressed wild-type E-cadherin and various E-cadherin mutants in invasive E-cadherin–negative human breast (MDA-MB-231) and prostate (TSU-Pr1) epithelial carcinoma cell lines using a tetracycline-inducible system. Our data confirm that E-cadherin inhibits human mammary and prostate tumor cell invasion. We find that adhesion is neither necessary nor sufficient for suppressing cancer invasion. Rather, the invasion suppressor signal is mediated through the β-catenin–binding domain of the E-cadherin cytoplasmic tail but not through the p120ctn-binding domain. β-catenin depletion also results in invasion suppression. However, alteration in the β-catenin/TCF transcriptional regulation of target genes is not required for the invasion suppressor activity of E-cadherin, suggesting the involvement of other β-catenin–binding proteins.
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23 June 2003
Article|
June 16 2003
Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin
Alice S.T. Wong,
Alice S.T. Wong
Department of Cell Biology, University of Virginia, Charlottesville, VA 22908
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Barry M. Gumbiner
Barry M. Gumbiner
Department of Cell Biology, University of Virginia, Charlottesville, VA 22908
Search for other works by this author on:
Alice S.T. Wong
Department of Cell Biology, University of Virginia, Charlottesville, VA 22908
Barry M. Gumbiner
Department of Cell Biology, University of Virginia, Charlottesville, VA 22908
Address correspondence to Barry M. Gumbiner, Dept. of Cell Biology, School of Medicine, University of Virginia, PO Box 800732, Charlottesville, VA 22903. Tel.: (434) 243-9290. Fax: (434) 924-2794. E-mail: [email protected]
Alice Wong's present address is Department of Zoology, University of Hong Kong, 4S-14 Kadoorie Biological Sciences Bldg., Pokfulam Rd., Hong Kong.
*
Abbreviations used in this paper: LEF, leukocyte enhancer factor; NS, nonspecific; rtTA, reverse tetracycline-responsive transcriptional activator; siRNA, small interfering RNA; TCF, T cell factor.
Received:
December 03 2002
Revision Received:
May 08 2003
Accepted:
May 08 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2003
J Cell Biol (2003) 161 (6): 1191–1203.
Article history
Received:
December 03 2002
Revision Received:
May 08 2003
Accepted:
May 08 2003
Citation
Alice S.T. Wong, Barry M. Gumbiner; Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin . J Cell Biol 23 June 2003; 161 (6): 1191–1203. doi: https://doi.org/10.1083/jcb.200212033
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