Remodeling of the extracellular matrix by serine proteases as a prerequisite for cancer initiation and progression
Tomasz Wenta, Paulina Nastały, Barbara Lipińska, Aki Manninen
Abstract
• ECM architecture is dynamically altered by serine proteases during carcinogenesis • Protease-mediated proteolysis modulates activities of ECM components and integrins • Degradation of ECM allows epithelial cancer cells to enter the blood circulation • ECM remodeling causes the release of many ECM-associated growth factors The extracellular matrix (ECM) serves as a physical scaffold for tissues that is composed of structural proteins such as laminins, collagens, proteoglycans and fibronectin, forming a three dimensional network, and a wide variety of other matrix proteins with ECM-remodeling and signaling functions. The activity of ECM-associated signaling proteins is tightly regulated. Thus, the ECM serves as a reservoir for water and growth regulatory signals. The ECM architecture is dynamically modulated by multiple serine proteases that process both structural and signaling proteins to regulate physiological processes such as organogenesis and tissue homeostasis but they also contribute to pathological events, especially cancer progression. Here, we review the current literature regarding the role of ECM remodeling by serine proteases (KLKs, uPA, furin, HtrAs, granzymes, matriptase, hepsin) in tumorigenesis.