Non-catalytic role for Mmp14 in stromal invasion Available to Purchase

During mammary gland branching morphogenesis, mammary epithelial cells (MECs) invade the surrounding stroma. Here (p. 343), Mina Bissell and co-workers investigate whether the matrix metalloproteinase Mmp14, which is expressed in mammary glands during branching and which has a key role in cancer cell invasion, is involved in branching morphogenesis. The researchers report that the catalytic activity of Mmp14 is required for MEC branching in dense but not sparse three-dimensional collagen gels, but that, surprisingly, a non-proteolytic function of Mmp14 is required for branching in both conditions. They show that silencing Mmp14 reduces the levels of integrin β1 (Itgb1), which is required for branching in vivo, and that Mmp14 associates directly with Itgb1 through a transmembrane/cytoplasmic domain in Mmp14. Notably, this non-catalytic domain is required for branching in collagen gels. These results indicate that non-proteolytic activities of Mmp14 modulate the Itgb1-dependent signals that mediate MEC invasion during branching...