J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/06/1103/14 $2.00
Volume 137, Number 5, June 2, 1997 1103-1116

Protein Kinase C Activation Upregulates Intercellular Adhesion of -Catenin-negative Human Colon Cancer Cell Variants via Induction of Desmosomes

Jolanda van Hengel,^* Lionel Gohon,^* Erik Bruyneel, Stefan Vermeulen, Maria Cornelissen,^§ Marc Mareel, and Frans van Roy^*

^* Department of Molecular Biology, Laboratory of Molecular Cell Biology, University of Ghent and Flanders Interuniversity Institute of Biotechnology (V.I.B.), B-9000 Ghent;  University Hospital Ghent, Department of Radiotherapy, Nuclear Medicine and Experimental Cancerology, B-9000 Ghent; and ^§ Department of Anatomy, Embryology, and Histology, University of Ghent, B-9000 Ghent, Belgium

The -catenin molecule links E-cadherin/ -catenin or E-cadherin/plakoglobin complexes to the actin cytoskeleton. We studied several invasive human colon carcinoma cell lines lacking -catenin. They showed a solitary and rounded morphotype that correlated with increased invasiveness. These round cell variants acquired a more normal epithelial phenotype upon transfection with an -catenin expression plasmid, but also upon treatment with the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Video registrations showed that the cells started to establish elaborated intercellular junctions within 30 min after addition of TPA. Interestingly, this normalizing TPA effect was not associated with -catenin induction. Classical and confocal immunofluorescence showed only minor TPA-induced changes in E-cadherin staining. In contrast, desmosomal and tight junctional proteins were dramatically rearranged, with a conversion from cytoplasmic clusters to obvious concentration at cell-cell contacts and exposition at the exterior cell surface. Electron microscopical observations revealed the TPA-induced appearance of typical desmosomal plaques. TPA-restored cell-cell adhesion was E-cadherin dependent as demonstrated by a blocking antibody in a cell aggregation assay. Addition of an antibody against the extracellular part of desmoglein-2 blocked the TPA effect, too. Remarkably, the combination of anti-E-cadherin and anti-desmoglein antibodies synergistically inhibited the TPA effect.

Our studies show that it is possible to bypass the need for normal -catenin expression to establish tight intercellular adhesion by epithelial cells. Apparently, the underlying mechanism comprises upregulation of desmosomes and tight junctions by activation of the PKC signaling pathway, whereas E-cadherin remains essential for basic cell-cell adhesion, even in the absence of -catenin.

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