Membrane-type serine protease 1 (MT-SP1) (MT-SP1)

Membrane-type serine protease 1 (MT-SP1), also known as matriptase, is a type II transmembrane serine protease (TTSP) that is widely expressed in the plasma membrane of epithelial cells (UniProt P56620). It is synthesized as a zymogen and undergoes autoactivation, a process tightly regulated by its cognate inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1) (List et al., 2006). MT-SP1 plays a vital role in maintaining epithelial integrity and is involved in the activation of several signaling molecules, including hepatocyte growth factor (HGF) and protease-activated receptor 2 (PAR-2) (Sanders et al., 2014). In various cancers, MT-SP1 is frequently overexpressed or dysregulated, promoting tumor cell proliferation, invasion, and metastasis by degrading the extracellular matrix and activating growth factors (Oberst et al., 2001). Consequently, it has emerged as a significant therapeutic target for the development of protease inhibitors aimed at treating solid tumors. Beyond oncology, mutations in the gene encoding MT-SP1 (ST14) are associated with skin disorders such as autosomal recessive ichthyosis with hypotrichosis (Alef et al., 2009). Therapeutic strategies targeting MT-SP1 include small molecule inhibitors and monoclonal antibodies designed to block its proteolytic activity (Zuo et al., 2021).

Other names

MatriptaseST14Suppressor of tumorigenicity 14 proteinSerine protease 14PRSS14TADG-15Epithin

Inhibition of the catalytic activity of the serine protease domain to prevent the activation of pro-oncogenic substrates and degradation of the extracellular matrix.