The EGFR (epidermal growth factor receptor) plays a key role in the regulation of essential normal cellular processes and in the pathophysiology of hyperproliferative diseases such as cancer. Recent investigations have demonstrated that GPCRs (G-protein-coupled receptors) are able to utilize the EGFR as a downstream signalling partner in the generation of mitogenic signals. This cross-talk mechanism combines the broad diversity of GPCRs with the signalling capacities of the EGFR and has emerged as a general concept in a multitude of cell types. The molecular mechanisms of EGFR signal transactivation involve processing of transmembrane growth factor precursors by metalloproteases which have been recently identified as members of the ADAM (adisintegrin and metalloprotease) family of zinc-dependent proteases. Subsequently, the EGFR transmits signals to prominent downstream pathways, such as mitogen-activated protein kinases, the phosphoinositide 3-kinase/Akt pathway and modulation of ion channels. Analysis of GPCR-induced EGFR activation in more than 60 human carcinoma cell lines derived from different tissues has demonstrated the broad relevance of this signalling mechanism in cancer. Moreover, EGFR signal transactivation was linked to diverse biological processes in human cancer cells, such as cell proliferation, migration and anti-apoptosis. Together with investigations revealing the importance of this GPCR–EGFR cross-talk mechanism in cardiac hypertrophy, Helicobacter pylori-induced pathophysiological processes and cystic fibrosis, these findings support an important role for GPCR ligand-dependent EGFR signal transactivation in diverse pathophysiological disorders.
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December 2003
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Conference Article|
December 01 2003
EGFR signal transactivation in cancer cells
O.M. Fischer;
O.M. Fischer
Max-Planck-Institute of Biochemistry, Department of Molecular Biology, Am Klopferspitz 18A, 82152 Martinsried, Germany
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S. Hart;
S. Hart
Max-Planck-Institute of Biochemistry, Department of Molecular Biology, Am Klopferspitz 18A, 82152 Martinsried, Germany
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A. Gschwind;
A. Gschwind
1
Max-Planck-Institute of Biochemistry, Department of Molecular Biology, Am Klopferspitz 18A, 82152 Martinsried, Germany
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A. Ullrich
A. Ullrich
2
Max-Planck-Institute of Biochemistry, Department of Molecular Biology, Am Klopferspitz 18A, 82152 Martinsried, Germany
2To whom correspondence should be addressed (e-mail ullrich@biochem.mpg.de).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2003 Biochemical Society
2003
Biochem Soc Trans (2003) 31 (6): 1203–1208.
Citation
O.M. Fischer, S. Hart, A. Gschwind, A. Ullrich; EGFR signal transactivation in cancer cells. Biochem Soc Trans 1 December 2003; 31 (6): 1203–1208. doi: https://doi.org/10.1042/bst0311203
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