Human epidermal growth factor receptor (EGFR) has been implicated in multiple cancers of epithelial derivation. EGFR is a transmembrane receptor kinase that spans the cell membrane and is activated by a number of external ligands, including EGF and transforming growth factor α. Activation of EGFR initiates several signal transduction cascades, leading to DNA synthesis and cell proliferation. There is one orthologous gene in flies, Dmel\Egfr, for which classical amorphic and hypomorphic alleles, constitutively active alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\Egfr is orthologous to three additional human genes, ERBB4, ERBB3 and ERBB2. ERBB2 has also been implicated in multiple cancers.
When Dmel\Egfr overexpression in imaginal disc epithelial cells is combined with expression of specific microRNAs (mir-ban, mir-8, mir-10 and mir-375), much more severe phenotypes are observed, including loss of apico-basal polarity and loss of epithelial organization, indicating an epithelial to mesenchymal transition. Reducing expression of one of the genes postulated to be the downstream regulatory targets of the microRNAs (for example, Socs36E and psq), in combination with Dmel\Egfr overexpression also results in more severe phenotypes; metastatic phenotypes are observed. See the human disease model reports 'cancer, epithelial, EGFR-Dmel\psq model' (FBhh0000933) and 'cancer, epithelial, EGFR-SOCS-related' (FBhh0000934).
Amorphic mutations of Dmel\Egfr act as recessive embryonic lethals; they also act as cell lethals in somatic clones. Hypermorphic (gain-of-function) alleles exhibit dominant visible phenotypes. Egfr overexpression in imaginal disc epithelial cells leads to mild overproliferation phenotypes. Extensive physical and genetic interactions have been described; see below and in the gene report for Egfr. See the human disease model report 'cancer, epithelial, EGFR-related' (FBhh0000932).
The human gene Hsap\EGFR has been introduced into flies, using a mutant form that displays constitutive kinase activity and can be expressed in specific tissues using the GAL4-UAS system. Constructs of Hsap\EGFR have been used for human disease models of malignant glioma (FBhh0000399, FBhh0000401, FBhh0000403).
[updated Dec. 2018 by FlyBase; FBrf0222196]
Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase of the ErbB family. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Binding of DGFR can activate at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. [from Gene Cards, EGFR; 2016.09.30]
Many to one (4 human to 1 Drosophila); additional human orthologs are ERBB4, ERBB3, and ERBB2.