 Plasmin is a powerful serine protein involved in numerous physiological processes, including embryonic development, thrombolysis, wound healing, and cancer progression. It is tightly regulated through activation of its precursor, plasminogen, only at specific times and locations, as well as through inhibition of active plasmin by its abundant natural inhibitors. Malignant cells can take advantage of the plasminogen activating system to increase plasmin production, which then modifies the tumor microenvironment to promote cancer progression. In addition to its role in degrading extracellular matrix proteins, plasmin also releases growth factors and cytokines from the stroma, as well as activates matrix metalloproteinase simogens, which have been studied extensively. However, recent evidence suggests that plasmin may also be able to cleave transmembrane molecules and induce outside-in-signal transduction, which could provide new insights into how cancer cells interact with their environment. This article was authored by Elena Ideriyugina and James P. Quigley. We are article.tv, links in the description below.