Role of convertases in cancer development and metastasis

Abstract

Convertases are serine proteases responsible for the maturation of inactive proproteins. To date, there are eight types of converters described PC1, PC2, Furine, PC4, PC5, PACE4, PC7, SKI-1 and PCSK9. The functions they perform are very diverse and, to a large extent, indispensable. Therefore, any alteration in their expression affects homeostasis and leads to pathologies. The involvement of PCSK9 in hypercholesterolemia and the involvement of Furine in 2019-NCoV infection should be noted. One of the pathologies in which the involvement of convertases has been most studied is the development of tumours. Their involvement in the maturation of adhesion molecules, metalloproteases and proinflammatory molecules, all of which are involved in tumour development, has been described. On the other hand, it has been observed that, when certain convertases are inhibited, the formation of tumours is slowed down, which shows their involvement in this process. Likewise, convertases are present in the tumour microenvironment, specifically in Liver sinusoidal endothelial cells (LSEC). Recently, the variation in the expression of PACE4 and PCSK9 convertases in this cell type when it comes into contact with media derived from metastatic colon tumour cells has been described. This observation opens the door to study the involvement of convertases in the hepatic metastasis process and suggests that these proteins could be a new therapeutic target.