Matrix-Degrading Type II Transmembrane Serine Protease Matriptase: Its Role in Cancer Development and Malignancy

Abstract

Proteolysis on the cell surface has well-known roles in the tissue homeostasis and in the pathogenesis such as cancers. A newly described, epithelia-derived type II transmembrane serine protease, matriptase, has been shown with important roles in the epithelial homeostasis, i.e., terminal keratinocyte differentiation, as well as its deregulation in the cancer development and progression. In epithelia, matriptase has a cognate inhibitor HAI-1 (hepatocyte growth factor activator inhibitor-1) for the regulation of this protease expression, trafficking, and activity. In animal model, matriptase is essential for postnatal survival, epidermal barrier function, stratum corneum, and hair follicle development, as well as thymocyte survival. Deregulated matriptase induces carcinogenesis and malignant transformation. In human cancers, both matriptase and HAI-1 expression are recurrently lost of their balance, resulting in activation of the protease, which is correlated with clinical stages. Thus, malfunction of matriptase potently raises cancer development and metastatic cancer lesions.