Matrix metalloproteinases target protease-activated receptors on the tumor cell surface

Matrix metalloproteinases, or MMPs, have been implicated in tumor invasion and metastasis by virtue of their ability to degrade the extracellular matrix (ECM) barrier. However, MMPs are also capable of cleaving non-ECM molecules. The protease-activated receptors (PARs) are the latest MMP targets. The thrombin receptor PAR1 has now been shown to be cleaved and activated on the tumor cell surface by stromal-derived MMP1. The resulting PAR1 activates intracellular G proteins to turn on the migratory and invasive program in tumor cells. This MMP-PAR axis may represent a novel signaling pathway communicating between tumor and stromal cells during tumor progression.