FB2026_02 , released June 18, 2026
Human Disease Model Report: cancer, germline stem cell models
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General Information
Name
cancer, germline stem cell models
FlyBase ID
FBhh0000768
Disease Ontology Term
Parent Disease
OMIM
Overview

Drosophila germline stem cells (GSCs) provide accessible model systems to study stem cell behavior, including the roles of stem cell competition, niche maintenance, and niche occupancy.

A screen of aged Drosophila males has shown development of spontaneous tumors in the testis and gut; the incidence of these tumors increases with age. In the testis, loss of activity of the Drosophila gene Madm (orthologous to the human NRBP1 and NRBP2 genes) or constitutive activity of Dmel\hop (orthologous to human JAK genes) have been found to promote GSC tumor formation.

In ovaries, loss-of-function mutations of bam, which encodes a translation repressor, have been used to produce tumor-like stem cells. The role of autophagy has been studied in this system. Reduced function of Sxl or other genes involved in RNA processing of bam gives rise to the GSC tumor phenotype. Expression of bam in the cystoblast requires cell–cell communications elicited by the bone morphogenetic proteins (BMPs) from the somatic cells in the germarium; disruption of BMP signaling (FBgg00010860) results in ovarian germline tumor formation.

Drosophila adult stem cells have been found to be resistant to radiation- or chemical-induced apoptosis, thus providing a means to investigate mechanisms of resistance of stem cell tumors to various anticancer therapies. In a study using ovary germline stem cells, irradiation results in activation of a specific receptor tyrosine kinase (Dmel\Tie), which then results in upregulation of the microRNA mir-ban and the repression of apoptosis.

[updated Feb. 2022 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, germline stem cell models
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 (4)
        Gene Groups / Pathways
        Comments on ortholog(s)

        Moderate- to high-scoring ortholog of human NRBP1 and NRBP2 (1 Drosophila to 2 human). Dmel\Madm shares 49-50% identity and 64-66% 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
        hopscotch (hop) encodes a non-receptor tyrosine kinase for interleukin-like ligands (encoded by upd1, upd2, and upd3) and functions in the JAK-STAT signaling pathway. It is involved in embryonic segmentation, cell proliferation, and cell migration. [Date last reviewed: 2019-03-07]
        Gene Groups / Pathways
        Comments on ortholog(s)

        Moderate-scoring ortholog of human JAK1 and JAK2; low-to-moderate-scoring ortholog of human TYK2 and JAK3 (1 Drosophila to 4 human); additional lower scoring orthologs exist in humans. Dmel\hop shares 24% identity and 39-41% similarity with JAK1 and JAK2.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Gene Snapshot
        bag of marbles (bam) encodes a protein involved in gametogenesis that is associated with the fusome, a germ cell-specific organelle. It contributes to the fate determination of germline stem cells, in which bam is negatively regulated by the BMP signaling pathway. [Date last reviewed: 2019-03-07]
        Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        No gene orthologous to Dmel\bam has been identified in human.

        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
          Other Genes Used: Viral, Bacterial, Synthetic (0)
            Summary of Physical Interactions (67 groups)
            protein-protein
            Interacting group
            Assay
            References
            two hybrid, anti tag coimmunoprecipitation, western blot, affinity technology, Identification by mass spectrometry
            RNA-protein
            Interacting group
            Assay
            References
            anti tag coimmunoprecipitation, quantitative reverse transcription pcr
            protein-protein
            Interacting group
            Assay
            References
            experimental knowledge based
            experimental knowledge based
            enzymatic study, western blot, 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
            anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, anti tag western blot
            RNA-protein
            Interacting group
            Assay
            References
            iclip, partial RNA sequence identification
            anti bait coimmunoprecipitation, quantitative reverse transcription pcr
            anti tag coimmunoprecipitation, quantitative reverse transcription pcr
            anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, two hybrid, bimolecular fluorescence complementation, fluorescence microscopy, molecular sieving, pull down
            anti bait coimmunoprecipitation, quantitative reverse transcription pcr
            anti tag coimmunoprecipitation, western blot, quantitative reverse transcription pcr
            nucleic acid uv cross-linking assay, autoradiography
            clip, reverse transcription pcr
            RNA-RNA
            Interacting group
            Assay
            References
            anti tag western blot, fluorescence technology
            protein-protein
            Interacting group
            Assay
            References
            anti tag coimmunoprecipitation, anti tag western blot, two hybrid
            pull down, anti tag western blot, anti tag coimmunoprecipitation, two hybrid, three hybrid, molecular sieving, western blot, bimolecular fluorescence complementation, fluorescence microscopy
            anti tag coimmunoprecipitation, anti tag western blot, two hybrid, bimolecular fluorescence complementation, fluorescence microscopy, western blot
            anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, Identification by mass spectrometry
            two hybrid, anti tag coimmunoprecipitation, anti tag western blot, western blot
            anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, anti tag western blot, western blot
            anti tag coimmunoprecipitation, anti tag western blot, two hybrid
            anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, two hybrid, bimolecular fluorescence complementation, fluorescence microscopy, molecular sieving, pull down
            anti tag coimmunoprecipitation, western blot, quantitative reverse transcription pcr
            pull down, molecular weight estimation by staining, anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, anti tag western blot, pull down, Identification by mass spectrometry
            bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, western blot, three hybrid
            pull down, molecular weight estimation by staining, colocalization, fluorescence microscopy, inferred by author, anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, anti tag western blot
            molecular sieving, western blot
            anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot
            anti tag coimmunoprecipitation, anti tag western blot, two hybrid
            anti tag coimmunoprecipitation, anti tag western blot, western blot
            anti tag coimmunoprecipitation, Identification by mass spectrometry, anti bait coimmunoprecipitation, western blot
            anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, Identification by mass spectrometry
            RNA-protein
            Interacting group
            Assay
            References
            anti bait coimmunoprecipitation, northern blot, anti tag coimmunoprecipitation, nuclease footprinting, autoradiography, filter binding, competition binding, pull down, western blot
            anti tag coimmunoprecipitation, northern blot, filter binding, autoradiography
            anti tag coimmunoprecipitation, northern blot
            electrophoretic mobility shift assay, autoradiography, enzymatic study, anti tag coimmunoprecipitation, northern blot
            enzymatic study, northern blot
            anti bait coimmunoprecipitation, quantitative reverse transcription pcr, northern blot, anti tag coimmunoprecipitation
            anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation
            anti tag coimmunoprecipitation, quantitative reverse transcription pcr
            anti tag coimmunoprecipitation, northern blot, anti bait coimmunoprecipitation, fluorescence polarization spectroscopy, predetermined participant
            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
            fluorescence technology, immunohistochemistry, luminiscence technology, necessary binding region
            luminiscence technology, necessary binding region
            luminiscence technology, necessary binding region, immunohistochemistry
            luminiscence technology, necessary binding region
            luminiscence technology, necessary binding region, immunohistochemistry, western blot
            fluorescence technology
            Alleles Reported to Model Human Disease (Disease Ontology) (22 alleles)
            Models Based on Experimental Evidence ( 9 )
            Modifiers Based on Experimental Evidence ( 8 )
            Allele
            Disease
            Interaction
            References
            Models Based on Experimental Evidence ( 1 )
            Allele
            Disease
            Evidence
            References
            Modifiers Based on Experimental Evidence ( 1 )
            Allele
            Disease
            Interaction
            References
            model of  germ cell cancer
            is ameliorated by Atg173F5
            is ameliorated by Atg61
            is ameliorated by Cdk23
            is ameliorated by InR339
            Models Based on Experimental Evidence ( 2 )
            Allele
            Disease
            Evidence
            References
            Modifiers Based on Experimental Evidence ( 7 )
            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
            PM hybrid dysgenesis
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            loss of function allele
            X ray
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            loss of function allele
            gamma ray
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            loss of function allele
            gamma ray
            amorphic allele - genetic evidence
            ethyl nitrosourea
            loss of function allele
            gamma ray
            amorphic allele - genetic evidence
            X ray
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl nitrosourea
            amorphic allele - genetic evidence
            ethyl nitrosourea
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            loss of function allele
            gamma ray
            amorphic allele - genetic evidence
            X ray
            loss of function allele
            gamma ray
            amorphic allele - genetic evidence
            ethyl methanesulfonate
            amorphic allele - genetic evidence
            ethyl nitrosourea
            loss of function allele
            CRISPR/Cas9
            loss of function allele
            P-element activity
            P-element activity
            P-element activity
            Delta2-3 transposase
            amorphic allele - genetic evidence
            Delta2-3 transposase
            References (17)