Epidermal growth factor receptor (EGFR) signaling in cancer

Nicola Normanno*, Antonella De Luca, Caterina Bianco, Luigi Strizzi, Mario Mancino, Monica R. Maiello, Adele Carotenuto, Gianfranco De Feo, Francesco Caponigro, David S. Salomon

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1691 Scopus citations

Abstract

The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases (RTK). These trans-membrane proteins are activated following binding with peptide growth factors of the EGF-family of proteins. Evidence suggests that the EGFR is involved in the pathogenesis and progression of different carcinoma types. The EGFR and EGF-like peptides are often over-expressed in human carcinomas, and in vivo and in vitro studies have shown that these proteins are able to induce cell transformation. Amplification of the EGFR gene and mutations of the EGFR tyrosine kinase domain have been recently demonstrated to occur in carcinoma patients. Interestingly, both these genetic alterations of the EGFR are correlated with high probability to respond to anti-EGFR agents. However, ErbB proteins and their ligands form a complex system in which the interactions occurring between receptors and ligands affect the type and the duration of the intracellular signals that derive from receptor activation. In fact, proteins of the ErbB family form either homo- or hetero-dimers following ligand binding, each dimer showing different affinity for ligands and different signaling properties. In this regard, evidence suggests that cooperation of multiple ErbB receptors and cognate ligands is necessary to induce cell transformation. In particular, the growth and the survival of carcinoma cells appear to be sustained by a network of receptors/ligands of the ErbB family. This phenomenon is also important for therapeutic approaches, since the response to anti-EGFR agents might depend on the total level of expression of ErbB receptors and ligands in tumor cells.

Original languageEnglish (US)
Pages (from-to)2-16
Number of pages15
JournalGene
Volume366
Issue number1
DOIs
StatePublished - Jan 17 2006

Funding

This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.) (national and regional grants), and from Ministero della Salute (Grant 110/FSN2004) to N. Normanno.

Keywords

  • EGF
  • ErbB
  • Growth factors
  • Signal transduction

ASJC Scopus subject areas

  • Genetics

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