Figure 2.

Mechanism by which matrix metalloproteinases (MMPs) can affect branching morphogenesis. 1. Proteolytic digestion of extracellular matrix (ECM) would alter ECM-integrin tethering and ECM-integrin signalling [47-48]. 2. Cleavage of ECM may produce soluble ECM fragments containing morphogenic activity [49-54]. 3. ECM-sequestered factors may be released to produce morphogenic gradients or signalling [52-54]. 4. Loss of cell–cell adhesion molecules by MMPs would lead to epithelial-to-mesenchymal transition and increased invasiveness [55-57]. 5. Ligand or receptor shedding might initiate autocrine, juxtacrine, or paracrine morphogenic signalling [58-59].