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General Information
Name
cancer, epithelial, EGFR-microRNA-related
FlyBase ID
FBhh0000398
Disease Ontology Term
Parent Disease
OMIM
Overview

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]

Disease Summary Information
Disease Summary: cancer, epithelial, EGFR-microRNA-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

Epidermal growth factor receptor (EGFR) has been implicated in multiple cancers, including non-small-cell lung cancer (OMIM:211980). [from OMIM:131550; 2016.09.30]

Cellular phenotype and pathology
Molecular information

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]

External links
Disease synonyms
Search term: neoplastic phenotype(s)
cancer, multiple, EGFR-related
Search term: metastatic phenotype(s)
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one (4 human to 1 Drosophila); additional human orthologs are ERBB4, ERBB3, and ERBB2.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (5)
      Gene Snapshot
      Epidermal growth factor receptor (Egfr) encodes the transmembrane tyrosine kinase receptor for signaling ligands (encoded by grk, spi, vn, and Krn) in the TGFα family, which utilises the intracellular MAP kinase pathway. The product of Egfr contributes to growth regulation, cell survival and developmental patterning. [Date last reviewed: 2019-06-06]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Orthologous to human genes EGFR, ERBB4, ERBB3, and ERBB2 (1 Drosophila to 4 human). Dmel\Egfr shares 33-37% identity and 46-51% similarity with the human genes.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      In progress.Contributions welcome.
      Molecular function (GO)
        Cellular component (GO)
          Gene Groups / Pathways
            Comments on ortholog(s)

            Orthologous to human MIR375 (FBrf0242402).

            Orthologs and Alignments from DRSC
            DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
            Gene Snapshot
            In progress.Contributions welcome.
            Molecular function (GO)
              Cellular component (GO)
                Gene Groups / Pathways
                  Comments on ortholog(s)

                  Orthologous to human MIR10A and MIR10B (FBrf0242402).

                  Orthologs and Alignments from DRSC
                  DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
                  Gene Snapshot
                  In progress.Contributions welcome.
                  Molecular function (GO)
                    Cellular component (GO)
                      Gene Groups / Pathways
                      Comments on ortholog(s)

                      Orthologous to human MIR429, MIR200B, MIR200C and others (FBrf0242402).

                      Orthologs and Alignments from DRSC
                      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
                      Gene Snapshot
                      In progress.Contributions welcome.
                      Cellular component (GO)
                        Gene Groups / Pathways
                        Comments on ortholog(s)

                        5' seed sequence homologous to that of human MIR450B-3p (FBrf0242402).

                        Orthologs and Alignments from DRSC
                        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
                        Synthetic Gene(s) Used (0)
                        Summary of Physical Interactions (101 groups)
                        RNA-protein
                        Interacting group
                        Assay
                        References
                        rna three hybrid
                        protein-protein
                        Interacting group
                        Assay
                        References
                        anti tag coimmunoprecipitation, anti tag western blot, solid phase assay, tag visualisation by fluorescence
                        anti bait coimmunoprecipitation, western blot
                        anti bait coimmunoprecipitation, western blot
                        anti tag coimmunoprecipitation, peptide massfingerprinting
                        pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot
                        anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
                        anti tag coimmunoprecipitation, peptide massfingerprinting, pull down, western blot, two hybrid, anti bait coimmunoprecipitation
                        anti tag coimmunoprecipitation, western blot, pull down, anti tag western blot
                        anti tag coimmunoprecipitation, peptide massfingerprinting
                        anti tag coimmunoprecipitation, anti tag western blot, western blot, enzyme linked immunosorbent assay
                        anti tag coimmunoprecipitation, peptide massfingerprinting
                        anti tag coimmunoprecipitation, peptide massfingerprinting
                        anti tag coimmunoprecipitation, peptide massfingerprinting
                        anti tag coimmunoprecipitation, anti tag western blot
                        anti tag coimmunoprecipitation, peptide massfingerprinting
                        anti tag coimmunoprecipitation, peptide massfingerprinting
                        anti tag coimmunoprecipitation, anti tag western blot, western blot, pull down
                        pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot
                        anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot, two hybrid, anti bait coimmunoprecipitation
                        anti bait coimmunoprecipitation, western blot
                        surface plasmon resonance, solid phase assay, tag visualisation by fluorescence, x-ray crystallography
                        anti tag coimmunoprecipitation, peptide massfingerprinting
                        anti tag coimmunoprecipitation, anti tag western blot, two hybrid
                        two hybrid, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting
                        RNA-protein
                        Interacting group
                        Assay
                        References
                        anti bait coimmunoprecipitation, northern blot
                        RNA-protein
                        Interacting group
                        Assay
                        References
                        anti bait coimmunoprecipitation, northern blot
                        anti tag coimmunoprecipitation, northern blot
                        enzymatic study, autoradiography
                        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
                        fluorescence polarization spectroscopy, predetermined participant
                        anti bait coimmunoprecipitation, primer specific pcr
                        anti tag coimmunoprecipitation, primer specific pcr
                        RNA-RNA
                        Interacting group
                        Assay
                        References
                        quantitative reverse transcription pcr
                        quantitative reverse transcription pcr
                        quantitative reverse transcription pcr, luminiscence technology
                        luminiscence technology
                        luminiscence technology
                        quantitative reverse transcription pcr
                        quantitative reverse transcription pcr
                        luminiscence technology, necessary binding region
                        quantitative reverse transcription pcr
                        luminiscence technology
                        quantitative reverse transcription pcr, luminiscence technology
                        immunohistochemistry, fluorescence technology, necessary binding region
                        quantitative reverse transcription pcr, luminiscence technology, necessary binding region
                        quantitative reverse transcription pcr
                        quantitative reverse transcription pcr
                        quantitative reverse transcription pcr
                        quantitative reverse transcription pcr
                        quantitative reverse transcription pcr
                        quantitative reverse transcription pcr
                        luminiscence technology
                        fluorescence technology
                        immunohistochemistry, luminiscence technology, necessary binding region, fluorescence technology
                        quantitative reverse transcription pcr, fluorescence technology, luminiscence technology, necessary binding region
                        luminiscence technology, quantitative reverse transcription pcr
                        quantitative reverse transcription pcr, western blot, luminiscence technology
                        luminiscence technology, quantitative reverse transcription pcr, western blot
                        western blot, quantitative reverse transcription pcr, luminiscence technology
                        quantitative reverse transcription pcr, luminiscence technology
                        luminiscence technology, quantitative reverse transcription pcr
                        luminiscence technology
                        luminiscence technology
                        immunohistochemistry, luminiscence technology, necessary binding region
                        fluorescence technology
                        RNA-protein
                        Interacting group
                        Assay
                        References
                        filter binding, autoradiography, anti tag coimmunoprecipitation, northern blot
                        anti tag coimmunoprecipitation, northern blot
                        electrophoretic mobility shift assay, autoradiography, enzymatic study, anti tag coimmunoprecipitation, northern blot
                        enzymatic study, northern blot
                        anti bait coimmunoprecipitation, northern blot, anti tag coimmunoprecipitation, quantitative reverse transcription pcr
                        anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation
                        anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation, fluorescence polarization spectroscopy, predetermined participant
                        enzymatic study, northern blot
                        anti tag coimmunoprecipitation, northern blot
                        anti tag coimmunoprecipitation, northern blot
                        anti tag coimmunoprecipitation, northern blot
                        anti tag coimmunoprecipitation, northern blot
                        anti tag coimmunoprecipitation, northern blot
                        anti bait coimmunoprecipitation, primer specific pcr
                        anti tag coimmunoprecipitation, northern blot
                        RNA-RNA
                        Interacting group
                        Assay
                        References
                        luminiscence technology, necessary binding region
                        luminiscence technology, necessary binding region
                        luminiscence technology, fluorescence technology, necessary binding region, immunohistochemistry
                        luminiscence technology, necessary binding region
                        luminiscence technology, necessary binding region, immunohistochemistry
                        luminiscence technology, necessary binding region
                        western blot, immunohistochemistry, luminiscence technology, necessary binding region
                        fluorescence technology
                        Alleles Reported to Model Human Disease (Disease Ontology) (14 alleles)
                        Models Based on Experimental Evidence ( 2 )
                        Modifiers Based on Experimental Evidence ( 7 )
                        Models Based on Experimental Evidence ( 1 )
                        Allele
                        Disease
                        Evidence
                        References
                        Modifiers Based on Experimental Evidence ( 5 )
                        Genetic Tools, Stocks and Reagents
                        Sources of Stocks
                        Contact lab of origin for a reagent not available from a public stock center.
                        Bloomington Stock Center Disease Page
                        Selected mammalian transgenes
                        Allele
                        Transgene
                        Publicly Available Stocks
                        Selected Drosophila transgenes
                        Allele
                        Transgene
                        Publicly Available Stocks
                        RNAi constructs available
                        Allele
                        Transgene
                        Publicly Available Stocks
                        Selected Drosophila classical alleles
                        Allele
                        Allele class
                        Mutagen
                        Publicly Available Stocks
                        loss of function allele
                        ethyl methanesulfonate
                        loss of function allele
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        gamma ray
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        loss of function allele
                        ethyl methanesulfonate
                        loss of function allele
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        loss of function allele
                        ethyl methanesulfonate
                        loss of function allele
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        gamma ray
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        amorphic allele - genetic evidence
                        gamma ray
                        ethyl methanesulfonate
                        amorphic allele - genetic evidence
                        ethyl methanesulfonate
                        amorphic allele - molecular evidence
                        I-SceI
                        amorphic allele - molecular evidence
                        Delta2-3 transposase
                        amorphic allele - molecular evidence
                        FLPase
                        P-element activity
                        P-element activity
                        Delta2-3 transposase
                        amorphic allele - genetic evidence
                        Delta2-3 transposase
                        References (18)