Fig. 8. A schematic outlining the relationships between metalloproteinases, metalloproteinase inhibitors and regulators of -catenin signaling. In Timp3^+/+ setting, E-cadherin and GSK3 influence the cytoplasmic pool of -catenin, which can translocate into the nucleus and function as transcriptional co-activator for target genes, Ccnd1 (cyclin D1) and Mmp7. We propose that MMP and ADAM activity operates upstream of E-cadherin and GSK3 through yet unidentified mechanisms to influence the signaling pool of -catenin. In Timp3 deficient mammary epithelial cells, -catenin signaling activity is increased, leading to selective gene responses. These arise in a GSK3-dependent manner and are not influenced by E-cadherin blocking. (, increased expression or activity; , decreased expression or activity; , unchanged expression or activity.)