Novel insights into cadherin processing by subtilisin-like convertases
Authors
Posthaus H, Dubois CM, Müller E.
Institution
Institute of Animal Pathology, University of Bern, Laenggass Str. 122, 3012 Bern
Country
Switzerland
Year
2003
Journal
FEBS Letters
Abstract
Proprotein convertases (PCs) are known to activate many important molecules and their overexpression plays a significant role in tumor progression. Only little is known about the involvement of PCs in the processing of cadherin adhesion molecules, which are potent tumor suppressors. Here we show in a baculovirus overexpression system that the desmosomal cadherins Dsg1 and Dsg3 are substrates for the PC furin. Accordingly, inhibition of PCs in differentiating mouse keratinocytes by alpha 1-anti-trypsin Portland (alpha 1-PDX) negatively interfered with pro-epithelial (proE)-cadherin processing, but unexpectedly also resulted in a dramatic reduction of E-cadherin, Dsg1 and Dsg3 protein and Dsg1 mRNA. Because loss of intercellular adhesion is a rate-limiting step in the transition from benign to malignant tumors, these results have significant implications for the use of PC inhibitors as possible therapeutic tools.