FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: cancer, epithelial, EGFR-microRNA-related
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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 (MIM:211980). [from MIM: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
cancer, multiple, EGFR-related
Search term: metastatic phenotype(s)
Search term: neoplastic 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
      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
      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
          Other Genes Used: Viral, Bacterial, Synthetic (0)
            Summary of Physical Interactions (110 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
            anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation
            pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
            two hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting, anti bait coimmunoprecipitation, western blot, pull down
            anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, western blot, pull down, anti tag 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
            pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot
            anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot
            pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, two hybrid
            anti bait coimmunoprecipitation, western blot
            cosedimentation in solution, solid phase assay, tag visualisation by fluorescence, surface plasmon resonance, x-ray crystallography, predetermined participant
            anti tag coimmunoprecipitation, peptide massfingerprinting
            anti tag coimmunoprecipitation, anti tag western blot, two hybrid
            anti bait coimmunoprecipitation, western blot, two hybrid, anti tag coimmunoprecipitation, peptide massfingerprinting
            RNA-protein
            Interacting group
            Assay
            References
            anti bait coimmunoprecipitation, northern blot, anti tag coimmunoprecipitation, filter binding, competition binding, autoradiography, pull down, western blot, nuclease footprinting
            anti tag coimmunoprecipitation, northern blot, filter binding, autoradiography
            anti tag coimmunoprecipitation, northern blot
            anti tag coimmunoprecipitation, northern blot, electrophoretic mobility shift assay, autoradiography, enzymatic study
            enzymatic study, northern blot
            anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
            anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation
            anti tag coimmunoprecipitation, quantitative reverse transcription pcr
            fluorescence polarization spectroscopy, predetermined participant, anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation
            enzymatic study, northern blot
            anti tag coimmunoprecipitation, northern blot
            anti tag coimmunoprecipitation, quantitative reverse transcription pcr
            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
            pull down, western blot
            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
            western blot, luminiscence technology, necessary binding region, immunohistochemistry
            fluorescence technology
            RNA-protein
            Interacting group
            Assay
            References
            anti bait coimmunoprecipitation, northern blot, pull down, western blot
            anti tag coimmunoprecipitation, northern blot
            enzymatic study, autoradiography
            anti bait coimmunoprecipitation, quantitative reverse transcription pcr
            anti tag 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
            pull down, western blot
            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
            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
            luminiscence technology, necessary binding region, immunohistochemistry, fluorescence technology
            quantitative reverse transcription pcr, fluorescence technology, luminiscence technology, necessary binding region
            quantitative reverse transcription pcr, luminiscence technology
            luminiscence technology, western blot, quantitative reverse transcription pcr
            western blot, luminiscence technology, quantitative reverse transcription pcr
            luminiscence technology, western blot, quantitative reverse transcription pcr
            luminiscence technology, quantitative reverse transcription pcr
            quantitative reverse transcription pcr, luminiscence technology
            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) (31 alleles)
            Models Based on Experimental Evidence ( 6 )
            Modifiers Based on Experimental Evidence ( 16 )
            Allele
            Disease
            Interaction
            References
            Models Based on Experimental Evidence ( 2 )
            Allele
            Disease
            Evidence
            References
            Modifiers Based on Experimental Evidence ( 7 )
            Models Based on Experimental Evidence ( 1 )
            Allele
            Disease
            Evidence
            References
            Modifiers Based on Experimental Evidence ( 3 )
            Models Based on Experimental Evidence ( 1 )
            Modifiers Based on Experimental Evidence ( 1 )
            Allele
            Disease
            Interaction
            References
            Alleles Representing Disease-Implicated Variants
            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
            Related mammalian, viral, bacterial, or synthetic 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
            ends-out gene targeting
            amorphic allele - molecular evidence
            ends-out gene targeting
            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 (21)