Matriptase: Potent Proteolysis on the Cell Surface

Matriptase was a type II transmembrane serine protease crucial for epidermal barrier function, hair follicle growth, and thymocyte survival. Its activation involved complex proteolytic cleavages and interaction with the inhibitor HAI-1. Matriptase-deficient mice showed severe defects in epidermal barrier, hair growth, and increased thymocyte apoptosis, leading to perinatal mortality. Dysregulation of matriptase and HAI expression was linked to human cancers, with unopposed matriptase promoting carcinogenesis and metastasis in animal models. While matriptase was consistently expressed in various epithelial tumors, its expression varied across cancers, complicating its use as a prognostic marker. Inhibition of matriptase impaired tumor cell invasion, highlighting its role in malignant progression. Despite advances, many questions about its precise functions and mechanisms remained unanswered.