E-cadherin immobilizes cells from the inside

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 β-catenin–interacting domain, inhibited the...