Protease Genomics and the Cancer Degradome

Abstract

Proteases comprise a large group of enzymes involved in multiple physiological and pathological processes, which has made necessary the introduction of global concepts for their study. Thus, the human degradome has been defined as the complete set of proteolytic genes encoded by the human genome. Likewise, the term cancer degradome defines the set of protease genes expressed by a tumour at a specific time. Detailed genomic analyses have revealed that the human degradome is composed of 569 protease-coding genes, whereas mouse and rat degradomes are even more complex, containing 649 and 634 genes, respectively. The precise knowledge of these differences is essential to understand the utility and limitations of these animal models to investigate human diseases, including cancer. In this regard, recent studies with genetically modified mice have shown that proteases contribute to all stages of tumour progression and not only to the later stages as was originally proposed. These studies have also revealed the existence of proteolytic enzymes with tumour-suppressive functions. Accordingly, any attempt to understand the biological and pathological relevance of proteases in cancer must take into account the large structural and functional diversity of proteolytic systems operating in all stages of the disease. Hopefully, the novel information derived from protease genomics may finally lead to the validation of some of these enzymes as important components of future strategies for cancer treatment.