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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
      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
        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
          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
                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
                      Synthetic Gene(s) Used (0)
                      Summary of Physical Interactions (103 groups)
                      RNA-protein
                      Interacting group
                      Assay
                      References
                      anti bait coimmunoprecipitation, quantitative reverse transcription pcr, clip-seq
                      rna three hybrid
                      protein-protein
                      Interacting group
                      Assay
                      References
                      solid phase assay, tag visualisation by fluorescence, anti tag coimmunoprecipitation, anti tag western blot
                      anti bait coimmunoprecipitation, western blot
                      anti bait coimmunoprecipitation, western blot
                      anti tag coimmunoprecipitation, peptide massfingerprinting
                      pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot
                      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
                      anti tag coimmunoprecipitation, peptide massfingerprinting, anti bait coimmunoprecipitation, western blot, pull down, two hybrid
                      pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot
                      anti tag coimmunoprecipitation, peptide massfingerprinting
                      enzyme linked immunosorbent assay, anti tag coimmunoprecipitation, western blot, anti tag western blot
                      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
                      anti tag coimmunoprecipitation, anti tag western blot, western blot, pull down
                      two hybrid, pull down, western blot, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, anti tag western blot
                      anti bait coimmunoprecipitation, western blot
                      surface plasmon resonance, x-ray crystallography, solid phase assay, tag visualisation by fluorescence
                      anti tag coimmunoprecipitation, peptide massfingerprinting
                      two hybrid, anti tag coimmunoprecipitation, anti tag western blot
                      anti tag coimmunoprecipitation, peptide massfingerprinting, two hybrid, anti bait coimmunoprecipitation, western blot
                      RNA-protein
                      Interacting group
                      Assay
                      References
                      anti tag coimmunoprecipitation, northern blot, filter binding, autoradiography
                      anti tag coimmunoprecipitation, northern blot
                      enzymatic study, autoradiography, electrophoretic mobility shift assay, anti tag coimmunoprecipitation, northern blot
                      enzymatic study, northern blot
                      anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
                      anti bait coimmunoprecipitation, northern blot, anti tag coimmunoprecipitation
                      anti bait coimmunoprecipitation, northern blot, fluorescence polarization spectroscopy, predetermined participant, anti tag coimmunoprecipitation
                      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
                      immunohistochemistry, luminiscence technology, necessary binding region
                      luminiscence technology, necessary binding region
                      immunohistochemistry, luminiscence technology, necessary binding region, western blot
                      fluorescence technology
                      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 tag coimmunoprecipitation, quantitative reverse transcription pcr
                      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
                      luminiscence technology, quantitative reverse transcription pcr
                      luminiscence technology
                      luminiscence technology
                      quantitative reverse transcription pcr
                      quantitative reverse transcription pcr
                      luminiscence technology, necessary binding region
                      quantitative reverse transcription pcr
                      luminiscence technology
                      luminiscence technology, quantitative reverse transcription pcr
                      fluorescence technology, necessary binding region, immunohistochemistry
                      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
                      luminiscence technology, necessary binding region, fluorescence technology, quantitative reverse transcription pcr
                      luminiscence technology, quantitative reverse transcription pcr
                      western blot, luminiscence technology, quantitative reverse transcription pcr
                      quantitative reverse transcription pcr, western blot, luminiscence technology
                      luminiscence technology, quantitative reverse transcription pcr, western blot
                      luminiscence technology, quantitative reverse transcription pcr
                      luminiscence technology, quantitative reverse transcription pcr
                      luminiscence technology
                      luminiscence technology
                      luminiscence technology, necessary binding region, immunohistochemistry
                      fluorescence technology
                      RNA-protein
                      Interacting group
                      Assay
                      References
                      anti bait coimmunoprecipitation, northern blot
                      Alleles Reported to Model Human Disease (Disease Ontology) (15 alleles)
                      Models Based on Experimental Evidence ( 2 )
                      Modifiers Based on Experimental Evidence ( 8 )
                      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 (19)