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General Information
Name
cancer, epithelial, SCRIB-hyperinsulinemia model
FlyBase ID
FBhh0001247
Disease Ontology Term
Parent Disease
OMIM
Overview

An established Drosophila model of cancer development in epithelial tissues makes use of somatic clones induced in developing imaginal discs. Somatic scrib(-) clones induced in developing eye imaginal discs in larvae are observed to have abnormal morphology and show increased proliferation; however, the scrib(-) clones are eliminated by cell competition when surrounded by wild-type cells and very little scrib(-) tissue is eventually observed in the adult eye (see FBhh0000587). In a genetic screen to identify genes that impact the cell-competition-based elimination of potentially tumorous clones, the Drosophila gene chico was identified. In animals heterozygous for chico, scrib(-) clones in the eye disc or in the wing disc evade cell competition and develop into tumors.

Dmel\chico encodes an insulin receptor substrate that is a core component of the Drosophila Insulin-like Receptor Signaling Pathway (see FBgg0000904 and FBgg0000910). Dmel\chico is orthologous to two human genes implicated in the development of insulin resistance and type 2 diabetes, IRS1 and IRS2 (see FBhh0000171). In flies, expression of chico in the insulin-producing cells (IPCs) of the brain was found to be necessary to maintain normal insulin levels. Reduced expression of chico specifically in the IPCs results in hyperinsulinemia and is sufficient to promote tumorous overgrowth of scrib(-) clones.

A diet-induced increase in insulin levels also triggers tumorigenesis in this system. The antidiabetic (antihyperglycemic) drug metformin was tested under the same dietary conditions and was found to suppress scrib(-) tumorigenesis.

[updated Aug. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, epithelial, SCRIB-hyperinsulinemia model
OMIM report
Human gene(s) implicated
Symptoms and phenotype

Epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer (Giovannucci et al, 2010; pubmed:20587728).

Increased cancer mortality associated with diabetes reflects both increased cancer incidence and decreased survival among people with diabetes who develop cancer (Diabetes Spectrum, https://spectrum.diabetesjournals.org/content/27/4/276).

Genetics
Cellular phenotype and pathology
Molecular information

IRS1 and IRS2 encode proteins that are phosphorylated by insulin receptor tyrosine kinase upon receptor stimulation; they may mediate the control of various cellular processes by insulin. [Gene Cards, IRS1, IRS2; 2020.08.23]

External links
Disease synonyms
cancer, epithelial, SCRIB-IRS-related
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 3 human gene to 1 Drosophila gene. The human genes are IRS1, IRS2, and IRS4.

    Human gene (HGNC)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    Many to one: 3 human gene to 1 Drosophila gene. The human genes are IRS1, IRS2, and IRS4.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      chico (chico) encodes a substrate of the product of InR. As a key component of the Insulin pathway, the chico product plays an essential role in the control of cell size and growth. [Date last reviewed: 2019-06-13]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate-scoring ortholog of human IRS1 and IRS2; low-scoring ortholog of IRS4 (1 Drosophila to 3 human). Dmel\chico shares 21-23% identity and 34-37% 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
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (28 groups)
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry
      anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      experimental knowledge based
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, peptide massfingerprinting, two hybrid, Identification by mass spectrometry, fluorescent resonance energy transfer
      experimental knowledge based
      fluorescent resonance energy transfer, anti tag coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry
      anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      anti tag coimmunoprecipitation, Identification by mass spectrometry
      experimental knowledge based
      experimental knowledge based
      Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
      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
      amorphic allele - molecular evidence
      P-element activity
      amorphic allele - molecular evidence
      P-element activity
      References (4)