FB2024_03 , released June 25, 2024
Human Disease Model Report: cancer, Malpighian tubule stem cell
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General Information
Name
cancer, Malpighian tubule stem cell
FlyBase ID
FBhh0001121
Disease Ontology Term
Parent Disease
OMIM
Overview

In insects, functions of the vertebrate kidneys are carried out by Malpighian tubules (MT) and nephrocytes [see 'kidney disease (fly models overview)' FBhh0000738]. In wild-type MTs, each stem cell generates one self-renewing and one differentiating daughter cell. However, if both daughter cells behave like stem cells, formation of hyperplastic tumors is observed. In a screen for mutations that affect MT stem cell self-renewal and differentiation, it was determined that loss of the polarity gene scribble (scrib) or of the Hippo signaling gene salvador (sav) increased proliferation. Stem cells expressing activated Ras (Ras85DV12) also exhibit increased proliferation, as well as reduced cell death and failure to differentiate; metastatic phenotypes are not observed.

In this system, the simultaneous loss of scrib does not further enhance the Ras85DV12 mutant phenotype. This is in contrast to systems modeling epithelial cancer initiation and progression in flies, in which expression of scrib loss-of-function alleles in combination with the Ras85DV12 activated mutation results in extensive tumors and metastatic phenotypes (see FBhh0000585).

[updated Oct. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, Malpighian tubule stem cell
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
    Disease synonyms
    Search term: hyperplastic phenotypes
    Ortholog Information
    Human gene(s) in FlyBase
      Other mammalian ortholog(s) used
        D. melanogaster Gene Information (1)
        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 (28 groups)
          protein-protein
          Interacting group
          Assay
          References
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          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
          pull down, two hybrid, anti tag coimmunoprecipitation, anti tag western blot
          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) (25 alleles)
          Models Based on Experimental Evidence ( 16 )
          Allele
          Disease
          Evidence
          References
          model of  cancer
          Modifiers Based on Experimental Evidence ( 17 )
          Allele
          Disease
          Interaction
          References
          model of  cancer
          is ameliorated by NetBΔ
          is ameliorated by NetBKK103672
          is ameliorated by InRGL00139
          is ameliorated by InRJF01183
          is ameliorated by InRJF01482
          is ameliorated by unc-5MI04273
          is ameliorated by TimpUAS.cPa
          is ameliorated by bskDN.UAS
          is ameliorated by bskHMS00777
          is exacerbated by hepAct.UAS
          is exacerbated by imdUAS.cGa
          is ameliorated by JraNIG.2275R
          ameliorates  cancer
          model of  kidney cancer
          is ameliorated by Pka-C1B3
          is ameliorated by mTorΔP
          model of  cancer
          is exacerbated by exe1
          is exacerbated by Ptp61FΔ
          is exacerbated by M6W186stop
          is ameliorated by Ptip3804
          is exacerbated by p53UAS.cUa
          is ameliorated by Ilp8MI00727
          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
          References (5)