Since Gross and Lapiere firstly discovered
matrix metalloproteinases (
MMPs) as important collagenolytic
enzymes during amphibian tadpole morphogenesis in 1962, this intriguing family of extracellular
proteinases has been implicated in various processes of developmental biology. However, the pathogenic roles of
MMPs in human diseases such as
cancer have also garnered widespread attention. The most straightforward explanation for their role in
cancer is that
MMPs, through extracellular matrix degradation, pave the way for
tumor cell invasion and
metastasis. While this notion may be true for many circumstances, we now know that, depending on the context,
MMPs may employ additional modes of functionality. Here, we will give an update on the function of
MMPs in development and
cancer, which may directly regulate signaling pathways that control tissue homeostasis and may even work in a non-proteolytic manner. These novel findings about the functionality of
MMPs have important implications for
MMP inhibitor design and may allow us to revisit
MMPs as drug targets in the context of
cancer and other diseases.