Novel insights into cadherin processing by subtilisin-like convertases |
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Authors: | Posthaus Horst Dubois Claire M Müller Eliane |
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Affiliation: | Institute of Animal Pathology, University of Bern, Laenggass Str. 122, 3012 Bern, Switzerland. |
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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. |
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