Remodeling of the extracellular matrix by serine proteases as a prerequisite for cancer initiation and progression

Abstract

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.