Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia

Abstract

When migrating away from a primary tumour, cancer cells interact with and remodel the extracellular matrix (ECM). Matrix metalloproteinases (MMPs), and in particular the transmembrane MT1-MMP (also known as MMP-14), are key enzymes in tumour-cell invasion. Results from recent in vitro studies highlight that MT1-MMP is implicated both in the breaching of basement membranes by tumour cells and in cell invasion through interstitial type-I collagen tissues. Remarkably, MT1-MMP accumulates at invadopodia, which are specialized ECM-degrading membrane protrusions of invasive cells. Here we review current knowledge about MT1-MMP trafficking and its importance for the regulation of protease activity at invadopodia. In invasive cells, endocytosis of MT1-MMP by clathrin- and caveolae-dependent pathways can be counteracted by several mechanisms, which leads to protease stabilization at the cell surface and increased pericellular degradation of the matrix. Furthermore, the recent identification of cellular components that control delivery of MT1-MMP to invadopodia brings new insight into mechanisms of cancer-cell invasion and reveals potential pharmacological targets.