FB2026_03 , released September 17, 2026
Human Disease Model Report: cancer, intestinal stem cell, RAS-NOTCH-related
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General Information
Name
cancer, intestinal stem cell, RAS-NOTCH-related
FlyBase ID
FBhh0001365
Disease Ontology Term
Parent Disease
OMIM
Overview

The Drosophila posterior midgut is closely analogous to the mammalian small intestine; the midgut epithelium is maintained by frequent division of self-renewing intestinal stem cells (ISCs). A model of intestinal cancer has been developed using ISC expression of an activated form of the Drosophila RAS gene Ras85D in combination with reduced expression of Notch (N), effected by RNAi.

Ras85D-N tumor growth correlates with an expansion of tracheal cell branching, similar to increased angiogenesis observed for human cancers. Using transplant of ISC tumor masses generated using this system, the role of btl (ortholgous to FGFR1-4 in human) has been assessed. btl is required for the process of tracheal remodeling observed in several ISC cancer models in flies.

See related human disease model reports cancer, intestinal stem cell, RAS-related (FBhh0001032) and cancer, intestinal stem cell, NOTCH-related (FBhh0001354).

[updated Jun. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, intestinal stem cell, RAS-NOTCH-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 Groups / Pathways
        Comments on ortholog(s)

        Moderate- to high-scoring ortholog of human NOTCH1, NOTCH2, NOTCH3, NOTCH4 (1 Drosophila to 4 human). Dmel\N shares 43-44% identity and 56-57% similarity with NOTCH1 and NOTCH2.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        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
        Other Genes Used: Viral, Bacterial, Synthetic (0)
          Summary of Physical Interactions (88 groups)
          protein-protein
          Interacting group
          Assay
          References
          two hybrid, enzyme linked immunosorbent assay
          anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, anti tag western blot, western blot
          anti bait coimmunoprecipitation, western blot
          proximity ligation assay, fluorescence microscopy
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, anti tag western blot
          pull down, western blot
          experimental knowledge based
          pull down, western blot, anti tag coimmunoprecipitation
          two hybrid, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, autoradiography
          proximity ligation assay, fluorescence microscopy
          affinity technology, tag visualisation by alkaline phosphatase activity
          pull down, autoradiography, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation
          anti bait coimmunoprecipitation, cross-linking study, western blot, enzyme linked immunosorbent assay, bead aggregation assay, fluorescence microscopy, inferred by author, affinity technology, atomic force microscopy, tag visualisation, tag visualisation by alkaline phosphatase activity, phenotype-based detection assay, pull down
          pull down, western blot, anti bait coimmunoprecipitation, two hybrid, autoradiography
          two hybrid, nuclear magnetic resonance, cosedimentation in solution, predetermined participant, anti tag coimmunoprecipitation, anti tag western blot, western blot
          anti tag coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy
          two hybrid, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot
          pull down, western blot, anti tag coimmunoprecipitation, two hybrid
          protease assay, western blot, inferred by author
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, peptide massfingerprinting, three hybrid, protein three hybrid
          two hybrid, anti bait coimmunoprecipitation, western blot
          pull down, western blot
          pull down, western blot
          pull down, western blot
          coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, western blot, pull down
          pull down, autoradiography, two hybrid
          anti tag coimmunoprecipitation, western blot, anti tag western blot
          anti tag coimmunoprecipitation, western blot
          experimental knowledge based
          experimental knowledge based
          anti tag coimmunoprecipitation, anti tag western blot
          anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, western blot
          affinity technology, fluorescence microscopy, inferred by author, bead aggregation assay, tag visualisation by alkaline phosphatase activity, anti bait coimmunoprecipitation, cross-linking study, western blot, anti tag coimmunoprecipitation, confocal microscopy, pull down, tag visualisation
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, pull down
          pull down, molecular weight estimation by staining, isothermal titration calorimetry, predetermined participant, autoradiography, nuclear magnetic resonance, western blot
          isothermal titration calorimetry, predetermined participant, electron microscopy, two hybrid, protein three hybrid, pull down, autoradiography, anti tag coimmunoprecipitation, western blot, three hybrid, peptide massfingerprinting, anti bait coimmunoprecipitation, anti tag western blot, molecular sieving, molecular weight estimation by staining, coimmunoprecipitation, cosedimentation, electrophoretic mobility shift assay, electrophoretic mobility supershift assay
          anti tag coimmunoprecipitation, anti tag western blot
          two hybrid, pull down, western blot, anti tag coimmunoprecipitation
          anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, anti tag western blot
          anti bait coimmunoprecipitation, cross-linking study, western blot
          inferred by author, confocal microscopy, bead aggregation assay
          proximity ligation assay, fluorescence microscopy
          anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry, anti tag western blot
          RNA-protein
          Interacting group
          Assay
          References
          nucleic acid uv cross-linking assay, autoradiography, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
          pull down, quantitative reverse transcription pcr
          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
          Alleles Reported to Model Human Disease (Disease Ontology) (51 alleles)
          Models Based on Experimental Evidence ( 13 )
          Allele
          Disease
          Evidence
          References
          Modifiers Based on Experimental Evidence ( 22 )
          Allele
          Disease
          Interaction
          References
          is exacerbated by CatHMS00990
          is ameliorated by CatUAS.cUa
          is ameliorated by cncUAS.cSa
          is exacerbated by Sod2HMS00499
          is exacerbated by cncHMS00650
          is ameliorated by Sod2UAS.cMa
          ameliorates  carcinoma
          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
          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
          amorphic allele - genetic evidence
          Delta2-3 transposase
          loss of function allele
          spontaneous
          loss of function allele
          spontaneous
          amorphic allele - genetic evidence
          X ray
          loss of function allele
          X ray
          loss of function allele
          ethyl methanesulfonate
          amorphic allele - genetic evidence
          gamma ray
          loss of function allele
          X ray
          loss of function allele
          X ray
          loss of function allele
          X ray
          loss of function allele
          X ray
          loss of function allele
          ethyl methanesulfonate
          loss of function allele
          ethyl methanesulfonate
          amorphic allele - genetic evidence
          X ray
          loss of function allele
          X ray
          loss of function allele
          ethyl methanesulfonate
          loss of function allele
          loss of function allele
          X ray
          loss of function allele
          X ray
          loss of function allele
          ethyl methanesulfonate
          loss of function allele
          X ray
          loss of function allele
          X ray
          loss of function allele
          loss of function allele
          loss of function allele
          ethyl methanesulfonate
          loss of function allele
          X ray
          amorphic allele - genetic evidence
          loss of function allele
          spontaneous
          loss of function allele
          ethyl methanesulfonate
          loss of function allele
          X ray
          loss of function allele
          X ray
          loss of function allele
          ethyl methanesulfonate
          amorphic allele - genetic evidence
          loss of function allele
          loss of function allele
          P-element activity
          amorphic allele - genetic evidence
          References (7)