Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 331, Issue 2, Pages 222-231Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2010.04.008
Keywords
EGFR transactivation; Triple membrane passing signal; Ligand-dependency; Multiple mechanisms; Relevance in HNSCC
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About one decade ago has been demonstrated that G protein-coupled receptors (GPCRs) are able to utilize the epidermal growth factor (EGF) receptor (EGFR) as signalling intermediate. Thereby GPCRs are enabled to regulate cell growth, differentiation, and migration. A molecular mechanism for this process has been proposed that involves the activation of a distinct set of metalloproteases and the subsequent generation and release of particular members of the EGF peptide family which in turn activate the EGFR in an autocrine/paracrine manner. This model that allows GPCRs direct access to the signalling network of the EGFR family has emerged as a valid concept in a variety of cell types including cancer cells. The present review briefly summarizes the current knowledge but will be focussed on the ligand-dependency of EGFR transactivation. Several alternative mechanisms and novel aspects will be introduced. Using the example of head and neck squamous carcinoma, the potency of EGFR transactivation as a therapeutical target will be discussed. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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