The Diverse Pathways for Cell Surface MT1-MMP Localization in Migratory Cells

Controlled cell migration is an essential biological process in health, while uncontrolled cell migration contributes to disease progression. For cells to migrate through tissue, they must first degrade the extracellular matrix (ECM), which acts as a physical barrier to cell migration. A type I transmembrane-type matrix metalloproteinase, MT1-MMP, is the key enzyme involved in this process. It has been extensively shown that MT1-MMP promotes the migration of different cell types in tissue, including fibroblasts, epithelial cells, endothelial cells, macrophages, mesenchymal stem cells, and cancer cells. MT1-MMP is tightly regulated at different levels, and its localization to leading-edge membrane structures is an essential process for MT1-MMP to promote cellular invasion. Different cells display different motility-associated membrane structures, which contribute to their invasive ability, and there are diverse mechanisms of MT1-MMP localization to these structures. In this article, we will discuss the current understanding of MT1-MMP regulation, in particular, localization mechanisms to these different motility-associated membrane structures.