Role of subtilisin-like convertases in cadherin processing or the conundrum to stall cadherin function by convertase inhibitors in cancer therapy.

Abstract

Cadherins are a family of intercellular adhesion receptors. Produced as inactive precursors, they become functional adhesion molecules after proteolytic cleavage by subtilisin-like pro-protein convertases (PCs). Owing to their activation and assembly into multiprotein adhesion complexes at sites of cell contacts, adhesion-competent cadherins are prerequisite for tissue integrity. In recent years evidence has accumulated that intercellular junctions not only provide mechanical linkage, but in addition are potent modulators of signalling cascades. This infers a biological role to intercellular adhesion complexes that is significantly more complex and powerful. Currently, the broad implications of disturbances in somatic tissue adhesion components are only just beginning to emerge. Prominent examples of adhesion defects include autoimmune diseases, or tumour invasion and metastasis and malignant transformation. This review reports on our current knowledge of cadherin function and their maturation by pro-protein convertases, and puts special emphasis on the consequences of pro-protein convertase inhibition for epithelial tissue homeostasis.