Remodeling of the extracellular matrix is a key process in cancer invasion. Matrix metalloproteases (MMPs) have been shown to be important in ECM remodeling but identifying individual MMPs with specific roles in various cancers has been difficult due to functional overlap with other proteases. The current Diseases Models and Mechanisms has an interesting article by Hald et al. in which they demonstrate that double-knockout mice lacking both plasmin and MMP-9 develop inflammatory colonic mass lesions that resemble mucosal prolapse lesions in humans. In contrast, wound healing in skin in these mice is normal. The findings indicate tissue-specific differences in ECM remodeling--and thus potential therapeutic targets. Further, this study demonstrates the potential utility of other mouse models for studying ECM remodeling in other tumors. Provocative stuff and more of the EMT story unravels.