© The Rockefeller University Press,
0021-9525/1997//1103 $5.00
The Journal of Cell Biology, Volume 137, Number 5,
, 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/ β-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.
Abbreviations used in this paper: PKC, protein kinase C; TPA, 12-O- tetradecanoyl-phorbol-13-acetate.
J. van Hengel is a Research Assistant with the Belgian National Fund for Scientific Research (NFSR), L. Gohon was supported by the Human Capital and Mobility Program of the E.U., and F. van Roy is Research Director with the NFSR. This research was supported by the Belgian Cancer Association; "Geconcentreerde Onderzoekacties," University of Ghent, Belgium; "Sportvereniging tegen Kanker," Belgium.
Please address all correspondence to Frans van Roy, University of Ghent and V.I.B., Department of Molecular Biology, Laboratory of Molecular Cell Biology, Ledeganckstraat 35, B-9000 Ghent, Belgium. Tel.: (32) 9-2645017. Fax: (32) 9-264-5331. e-mail: f.vanroy{at}lmb1.rug.ac.be

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