Role of Serine Proteases and Inhibitors in Cancer

Abstract

Serine proteases, the largest human protease family, are found in many key developmental and physiological processes in the biological system. Protease signalling pathways are stringently controlled, and deregulation of proteolytic activity results in the degradation of extracellular matrix which plays a major role in cancer progression. The Type II transmembrane serine protease, hepsin, matriptase-2 and TMPRSS4, and secreted serine protease, urokinase plasminogen activator (uPA), kallikreins and HtrA, are closely related to cancer-associated proteases and also involved in perturbation of uPA plasminogen system, matrix metalloproteases (MMPs), upregulation of adhesion molecules like integrin family, activation of intracellular signalling cascade, inhibition of apoptosis pathway in various types of cancers which causes cell proliferation, invasion and metastasis. Serpin, an endogenous serine protease inhibitor, regulates the homeostasis by maintaining a delicate balance with the serine protease and prevents the process of invasion and metastasis of cancer cells thus inhibiting tumour growth. This chapter focuses on the role of serine proteases and their inhibitors in different types of tumours associated with cancer prognostication and therapy.