FB2026_03 , released September 17, 2026
Human Disease Model Report: cancer, epithelial, TNF-RAS-related
Open Close
General Information
Name
cancer, epithelial, TNF-RAS-related
FlyBase ID
FBhh0001605
Disease Ontology Term
Parent Disease
OMIM
Overview

A model of epithelial cancer using the Drosophila egr gene in combination with the Drosophila Ras85D gene has been developed. The role of CRK family proteins in cancer has been investigated using this and related systems.

The RAS proteins are GDP/GTP-binding proteins that act as intracellular signal transducers and are crucial players in many signaling networks affecting cell cycle progression, growth, migration, cytoskeletal changes, apoptosis, and senescence. Originally defined as oncogenes, the RAS GTPase family includes KRAS (MIM:190070), HRAS (MIM:190020), and NRAS (MIM:164790); mutations in these three genes are among the most common events in human cancers. For KRAS, HRAS and NRAS, there is a single high-scoring ortholog in Drosophila, Ras85D, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. There are multiple other paralogous and orthologous genes in both species.

Tumor necrosis factor (TNF) proteins are transmembrane proteins that can be released from the cell membrane by extracellular proteolytic cleavage; they can act via both autocrine and paracrine signaling. This is a large gene family in human; in Drosophila there is a single TNF gene, eiger (egr). Animals homozygous for the loss-of-function mutation of egr1 are viable and fertile, with minor feeding and immune response phenotypes.

[updated Nov. 2024 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, epithelial, TNF-RAS-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (2)
      Gene Snapshot
      Ras oncogene at 85D (Ras85D) encodes a protein that acts downstream of several cell signals, most notably from Receptor Tyrosine Kinases, to regulate tissue growth and development. When abnormally activated it can direct developmental defects and tissue hyperplasia, mimicking aspects of human disease including Rasopathies and cancer, respectively. [Date last reviewed: 2019-03-14]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human genes KRAS, HRAS, and NRAS (many to many; multiple paralogs and orthologs in both species). Dmel\Ras85D shares 78-86% identity and 86-92% similarity with KRAS, HRAS, and NRAS; for these three human genes, Ras85D is the highest-scoring ortholog in Drosophila.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      eiger (egr) encodes the TNF superfamily ligand that activates the intracellular JNK pathway through its receptor encoded by grnd or wgn. Its roles include cell death, tumor suppression, tumor promotion, growth regulation, host defense, pain sensitization, and nutrient response. [Date last reviewed: 2018-10-11]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Sole TNF family gene in Drosophila (1 Drosophila to many human); Dmel\egr is most closely related to human EDA, TNFSF13, and TNFSF13B.

      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 (36 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        pull down, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        two hybrid, anti tag coimmunoprecipitation, autoradiography
        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
        gtpase assay, autoradiography
        anti tag coimmunoprecipitation, peptide massfingerprinting
        two hybrid, pull down, western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        two hybrid, anti tag coimmunoprecipitation, anti tag western blot, pull down
        pull down, anti tag western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        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, Identification by mass spectrometry, pull down, covalent binding, western blot
        protein-protein
        Interacting group
        Assay
        References
        static light scattering
        pull down, western blot
        anti tag coimmunoprecipitation, anti tag western blot, pull down, molecular weight estimation by staining, x-ray crystallography, static light scattering, isothermal titration calorimetry, predetermined participant, molecular sieving
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot, molecular sieving, molecular weight estimation by staining, isothermal titration calorimetry, predetermined participant, static light scattering
        Alleles Reported to Model Human Disease (Disease Ontology) (37 alleles)
        Models Based on Experimental Evidence ( 17 )
        Allele
        Disease
        Evidence
        References
        model of  cancer
        Modifiers Based on Experimental Evidence ( 19 )
        Allele
        Disease
        Interaction
        References
        model of  cancer
        is exacerbated by ITPUAS.F
        model of  cancer
        is ameliorated by InRGL00139
        is ameliorated by InRJF01183
        is ameliorated by InRJF01482
        is ameliorated by NetBΔ
        is ameliorated by NetBKK103672
        is ameliorated by unc-5MI04273
        is ameliorated by JraNIG.2275R
        is ameliorated by bskDN.UAS
        is ameliorated by bskHMS00777
        is exacerbated by hepAct.UAS
        is exacerbated by imdUAS.cGa
        is ameliorated by TimpUAS.cPa
        ameliorates  cancer
        model of  kidney cancer
        is ameliorated by Pka-C1B3
        is ameliorated by mTorΔP
        model of  cancer
        is exacerbated by Ptp61FΔ
        is exacerbated by exe1
        is exacerbated by M6W186stop
        is ameliorated by Ptip3804
        is exacerbated by p53UAS.cUa
        is ameliorated by Ilp8MI00727
        is exacerbated by Clbn1Q
        exacerbates  carcinoma
        model of  carcinoma
        is exacerbated by NkapGD11807
        Models Based on Experimental Evidence ( 5 )
        Modifiers Based on Experimental Evidence ( 11 )
        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
        loss of function allele
        P-element activity
        amorphic allele - genetic evidence
        P-element activity
        Delta2-3 transposase
        amorphic allele - molecular evidence
        P-element activity
        amorphic allele - molecular evidence
        Delta2-3 transposase
        References (3)