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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.2 y! T. R* W* O4 N8 d; R
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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 ?-catenin–interacting domain, inhibited the invasive phenotype of the cells.1 K7 E. O6 p6 V% v1 x& k5 @& {
( x! G8 O0 _# N- ? `5 ?. v?-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 ?-catenin action by sequestering the protein from its target genes, and indeed the authors found that loss of ?-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 ?-catenin. This conundrum leaves the authors in search of another ?-catenin target, perhaps another transcription factor, that regulates invasiveness.(E-cadherin stops invasion by making cell) |
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发表于 2009-3-6 00:54
发表于 2015-6-17 21:01
