QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 25 November 2008
doi: 10.1242/jcs.027995

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.027995v1 121/24/4089    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rappl, A. Articles by Schlegel, J. Search for Related Content PubMed PubMed Citation Articles by Rappl, A. Articles by Schlegel, J. Social Bookmarking                         What's this?

EGFR-dependent migration of glial cells is mediated by reorganisation of N-cadherin

¹ Division of Neuropathology, Institute of Pathology, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany
² Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany

^* Author for correspondence (e-mail: schlegel{at}tum.de)

Accepted 9 September 2008

Receptor tyrosine kinases of the EGFR family exert their various effects on cellular function through the formation of different dimeric receptor complexes. To investigate the functional impact of EGFR-HER2 heterodimers on migration of glial tumour cells, we stably transfected different HER2 constructs, including a constitutively active (HER2VE) and a dominant-negative (HER2VEKA) receptor, in the EGFR-overexpressing human glioma cell line LN18. Interference of EGFR activation through HER2VEKA inhibited cellular migration, whereas EGFR activation through HER2VE increased migration. These results were corroborated by inhibition of EGFR-HER2 signalling with tyrosine kinase inhibitors, because only the blocking of both receptors in HER2VE-cells with the bi-specific inhibitor AEE788 downregulated migration to levels comparable with those in HER2VEKA cells. The non-migratory phenotype was mediated through upregulation of N-cadherin and its recruitment to the cell membrane in HER2VEKA cells; downregulation of N-cadherin by RNAi restored migration in HER2VEKA cells and N-cadherin was also downregulated in migrating HER2VE-cells. Downregulation of N-cadherin levels in the plasma membrane was accompanied by a direct interaction of the EGFR-HER2 and N-cadherin–β-catenin complexes, leading to tyrosine phosphorylation of β-catenin. These results indicate that HER2 affects glial-cell migration by modulating EGFR-HER2 signal transduction, and that this effect is mediated by N-cadherin.

Key words: Adhesion, Signal transduction, Cell morphology

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Rappl, G. Piontek, and J. Schlegel EGFR-dependent migration of glial cells is mediated by reorganisation of N-cadherin Development, January 1, 2009; 136(1): e1 - e1. [Full Text] [PDF]