Epidermal growth factor receptor (EGFR) signaling in cancer.
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.
Normanno
Nicola
N
Cell Biology and Preclinical Models Unit, INT-Fondazione Pascale, 80131 Naples, Italy. nicnorm@yahoo.com
De Luca
Antonella
A
Bianco
Caterina
C
Strizzi
Luigi
L
Mancino
Mario
M
Maiello
Monica R
MR
Carotenuto
Adele
A
De Feo
Gianfranco
G
Caponigro
Francesco
F
Salomon
David S
DS
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors