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General Information
Name
cancer, epithelial, EGFR-Dmel\psq model
FlyBase ID
FBhh0000933
Disease Ontology Term
Parent Disease
OMIM
Overview

This model of epithelial cancer combines overexpression of epidermal growth factor receptor (EGFR) with reduced expression of Dmel\psq, a gene involved in transcriptional regulation; no human ortholog of Dmel\psq has been identified. Interactions between tumorigenic epithelial cells and normal mesenchymal cells have been investigated using this disease model system.

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.

Amorphic mutations of Dmel\Egfr act as recessive embryonic lethals; they also act as cell lethals in somatic clones. Hypermorphic (gain-of-function) alleles result in dominant visible phenotypes. Egfr overexpression in imaginal disc epithelial cells leads to mild overproliferation phenotypes. Reducing expression of the Drosophila gene psq in combination with Dmel\Egfr overexpression results in more severe phenotypes: larvae fail to enter pupariation and the discs continue to grow, often filling the anterior half of the larva; metastatic phenotypes are observed. Dmel\psq was selected as a candidate for investigation based on the fact that the levels of expression of microRNAs mir-10 and mir-375 impact the EGFR phenotypes; the psq transcript is predicted to be a target of these two miRNAs.

See also the human disease model report 'cancer, epithelial, EGFR-microRNA-related' (FBhh0000398).

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-Dmel\psq model
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 EGFR 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)
Search term: cancer, epithelial-mesenchymal interactions
Search term: metastatic phenotype(s)
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (2)
      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
      pipsqueak (psq) encodes a transcription factor that regulates chromatin silencing. It mediates the interaction of Polycomb group (Pc-G) members with Pc-G response elements. [Date last reviewed: 2019-06-13]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)
      No gene orthologous to Dmel\psq has been identified in vertebrates.
      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 (44 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, western blot, anti tag coimmunoprecipitation
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, two hybrid, pull down
      pull down, anti tag western blot, western blot, anti tag coimmunoprecipitation
      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, western blot, pull down, anti tag western blot
      pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot
      two hybrid, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot, pull down
      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
      protein-protein
      Interacting group
      Assay
      References
      comigration in gel electrophoresis, anti tag western blot, molecular sieving, molecular weight estimation by staining, two hybrid
      bimolecular fluorescence complementation, fluorescence microscopy
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      pull down, western blot, anti bait coimmunoprecipitation
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      two hybrid, experimental knowledge based
      bimolecular fluorescence complementation, fluorescence microscopy
      Alleles Reported to Model Human Disease (Disease Ontology) (7 alleles)
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 4 )
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      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
      loss of function allele
      P-element activity
      loss of function allele
      P-element activity
      loss of function allele
      P-element activity
      loss of function allele
      P-element activity
      loss of function allele
      P-element activity
      loss of function allele
      P-element activity
      loss of function allele
      P-element activity
      loss of function allele
      Delta2-3 transposase
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      Delta2-3 transposase
      loss of function allele
      Delta2-3 transposase
      References (7)