Issues

Schematic depiction of how N-cadherin, a mesenchymal cell-cell adhesion molecule upregulated during malignant tumor progression, may mediate pro-invasive signaling. First, cell-cell adhesion to N-cadherin–expressing cells of the stroma. Second, binding and activation of FGF receptors (FGFR), which results in FGFR signaling and the promotion of cell survival, migration, and invasion. Third, cleavage and shedding of the extracellular domain of N-cadherin by ADAM metallopeptidase domain 10 (ADAM10). Shedded N-cadherin may neutralize N-cadherin–mediated cell-cell adhesion and/or stimulate FGFR signaling on neighboring cells. Fourth, cleavage of N-cadherin by γ-secretase results in the translocation of the C-terminal fragment of N-cadherin (CTF2) to the nucleus, where it binds CREB-binding protein (CBP), induces its degradation and thus modulates expression. For further details, please see Yilmaz and Christofori on page 629 in this issue.