Suppressor of tumorigenicity 14 (Matriptase) (ST14)

Activated matriptase refers to the mature, proteolytically active form of the Suppressor of tumorigenicity 14 (ST14) protein, a type II transmembrane serine protease (TTSP) essential for epithelial barrier integrity (UniProt P56620). Unlike its zymogen precursor, activated matriptase possesses a functional catalytic domain capable of processing substrates such as hepatocyte growth factor (HGF), prostasin, and protease-activated receptor 2 (PAR2), which drive cell proliferation and tissue remodeling (Uhland, 2006, Cell. Mol. Life Sci.). In many epithelial cancers, the regulation of matriptase activation is lost, leading to an accumulation of the active enzyme that promotes tumor invasion and metastasis (Sanders et al., 2019, Cancers). This active form is a primary therapeutic target, with drug development focusing on inhibitors and antibodies that specifically bind the catalytic domain or recognize neo-epitopes exposed only upon activation. However, targeting the active enzyme carries risks, as matriptase activity is required for normal skin physiology; its absence or inhibition can lead to autosomal recessive congenital ichthyosis (List et al., 2006, Genes & Dev). Consequently, the matriptase-to-HAI-1 ratio is a key biomarker for identifying tumors where activated matriptase is pathologically elevated. Clinical challenges include ensuring selectivity over other related serine proteases and managing potential dermatological side effects.

Other names

MatriptaseMembrane-type serine protease 1MT-SP1EpithinTumor-associated differential display gene 15 proteinTADG-15Serine protease 14Activated matriptase

Small molecule or antibody-mediated inhibition of the catalytic serine protease domain of the activated enzyme, preventing the proteolytic processing of substrates such as pro-HGF and PAR2 (Sanders et al., 2019).