Transmembrane protease serine 4: An emergent diagnostic biomarker and Therapeutic drug target for cancer

Abstract

Proteases expressed in healthy cells are significant for performing necessary biological functions. There exists equilibrium among proteases and anti-proteases in living systems, thus interruption of equilibrium results in numerous disorders such as cancer. One of the signs of cancer development is proteolysis due to dysregulation of proteases. All five categories of proteases including cysteine, aspartate, threonine, matrix metalloproteases and serine have been associated with solid tumor instigation, growth, development, invasiveness and metastasis. The set of genes expressed in neoplasm development is well-known as cancer ‘degradome’. Transmembrane protease serine 4 (TMPRSS4), a novel type II transmembrane serine protease present at the cellular membrane is upregulated in numerous kinds of human carcinoma and have an irreplaceable role in tumor development. Hepsin, matriptase and TMPRSS2 are other cancer-associated proteases interconnected to TMPRSS4.TMPRSS4 can be used as an emerging therapeutic drug target in human malignant neoplasms as over expression of TMPRSS4 contribute significantly in processes of cancer development including vascularization, metastasis and invasion. Nevertheless, the biological function of TMPRSS4 in solid tumors continues to be ambiguous. In this review, we will discuss about physiological function, gene expression, clinical significance and regulation mechanism of TMPRSS4 in cancer development. Our study provides the rationale for targeting TMPRSS4 in cancer.