Article
- The EMBO Journal (2008) 27, 2603 - 2615
- doi:10.1038/emboj.2008.178
Published online: 4 September 2008
Subject Categories:
NCAM-induced focal adhesion assembly: a functional switch upon loss of E-cadherin
Francois Lehembre1,a, Mahmut Yilmaz1, Andreas Wicki1, Tibor Schomber1, Karin Strittmatter1, Dominik Ziegler1, Angelika Kren1, Phillip Went2, Patrick WB Derksen3, Anton Berns4, Jos Jonkers3 and Gerhard Christofori1
- Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Basel, Switzerland
- Institute of Pathology, University of Basel, Basel, Switzerland
- Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
- Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Correspondence to:
Gerhard Christofori, Department of Biomedicine, Institute of Biochemistry and Genetics, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland. Tel.: +41 61 267 3562; Fax: +41 61 267 3566; E-mail: gerhard.christofori@unibas.ch
aPresent address: Actelion Pharmaceuticals Ltd, Allschwil, Switzerland
Received 22 February 2008; Accepted 12 August 2008
Abstract
Loss of expression of the cell–cell adhesion molecule E-cadherin is a hallmark of epithelial–mesenchymal transition (EMT) in development and in the progression from epithelial tumours to invasive and metastatic cancers. Here, we demonstrate that the loss of E-cadherin function upregulates expression of the neuronal cell adhesion molecule (NCAM). Subsequently, a subset of NCAM translocates from fibroblast growth factor receptor (FGFR) complexes outside lipid rafts into lipid rafts where it stimulates the non-receptor tyrosine kinase p59Fyn leading to the phosphorylation and activation of focal adhesion kinase and the assembly of integrin-mediated focal adhesions. Ablation of NCAM expression during EMT inhibits focal adhesion assembly, cell spreading and EMT. Conversely, forced expression of NCAM induces epithelial cell delamination and migration, and high NCAM expression correlates with tumour invasion. These results establish a mechanistic link between the loss of E-cadherin expression, NCAM function, focal adhesion assembly and cell migration and invasion.
Keywords:
- cancer,
- cell adhesion,
- E-cadherin,
- EMT,
- metastasis
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