Published online 16 June 2003. doi:10.1083/jcb1616iti3
© The Rockefeller University Press,
0021-9525/2003/6/1007 $5.00
The Journal of Cell Biology, Volume 161, Number 6, 1007-1007
E-cadherin immobilizes cells from the inside
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E-cadherin stops invasion by making cells sticky (left), but not if its intracellular domain is missing (right).
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As invasive cells, metastatic tumor cells must be free-roaming—able to detach from the extracellular matrix and neighboring cells. So when E-cadherin, a cell–cell adhesion molecule, was found to suppress invasion, it was logical to attribute this ability to its adhesive properties. But results by Wong and Gumbiner on page 1191 indicate that E-cadherin uses an adhesion-independent mechanism to inhibit the invasiveness of human cancer cells.
The authors studied the effects of various E-cadherin constructs on two invasive cell lines derived from breast and prostate cancers. They found that intracellular signaling, not adhesion, mediated E-cadherin's tumor suppressor function. The adhesive portion of E-cadherin, its extracellular domain, was neither necessary nor sufficient to stop invasive behavior. In contrast, constructs containing E-cadherin's cytoplasmic tail, in particular the ß-catenin–interacting domain, inhibited the invasive phenotype of the cells.
ß-Catenin, as part of the Wnt signaling pathway, activates transcription of a set of target genes that induce cell motility, including a matrix metalloproteinase. E-cadherin can suppress ß-catenin action by sequestering the protein from its target genes, and indeed the authors found that loss of ß-catenin also stopped invasion. However, invasion inhibition did not depend on transcription of known targets of TCF transcription factors, which are known to associate with ß-catenin. This conundrum leaves the authors in search of another ß-catenin target, perhaps another transcription factor, that regulates invasiveness. 
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin
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