FB2024_04 , released June 25, 2024
Human Disease Model Report: cancer, epithelial, RAF-SCRIB-related
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General Information
Name
cancer, epithelial, RAF-SCRIB-related
FlyBase ID
FBhh0001079
Disease Ontology Term
Parent Disease
OMIM
Overview

A model of epithelial cancer has been developed using the loss-of-function mutations of the Drosophila scrib gene in combination with a constitutively active form of the Drosophila Raf gene, assayed in the developing eye. See also the human disease model reports 'cancer, epithelial, SCRIB-related' (FBhh0000587), 'cancer, multiple, RAF1-related' (FBhh0000558), and 'cancer, epithelial, RAS-SCRIB-related' (FBhh0000585).

When induced in the developing eye during the larval stage, scrib(-) clones result in small benign lesions in the adult eye that appear undifferentiated and disorganized. Clones induced in the developing eye that express activated Raf (RafUAS.F179) develop into vigorously proliferating tissue during larval stages and ultimately overgrow much of the adult eye. This tissue overgrowth remains restricted to the tissues derived from the eye-antennal disc and is apparently not invasive; the animals survive until pharate adult stages. When clones containing the activated Raf allele combined with a loss-of-function mutation for scrib are induced, massive and invasive overgrowth occurs in larval stages, which kills the animal before pupation. Combining an additional element, an activated form of hep which results in increased JNK signaling, significantly, but not completely, suppresses the aggressive overgrowth.

This disease model has been used to investigate the disruption of zinc homeostasis that has been observed for various cancers.

[updated Apr. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, epithelial, RAF-SCRIB-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
      scribble (scrib) encodes a scaffolding protein that is part of the conserved machinery regulating apicobasal polarity. It acts with the products of dlg1 and l(2)gl to distinguish the basolateral domain of epithelial cells and neuroblasts, via reciprocally antagonistic interactions with the aPKC/par-6 complex that impacts vesicle trafficking. The product of scrib also organizes synaptic architecture and is implicated in learning and memory. [Date last reviewed: 2019-03-14]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Ortholog of human SCRIB and LRRC1 (1 Drosophila to 2 human); Dmel\scrib shares 33% identity and 45% similarity with the human SCRIB gene. The human LRRC1 gene encodes a much smaller protein, corresponding to the amino end of SCRIB and Dmel\scrib; it shares 57% identity and 73% similarity with Dmel\scrib within that extent.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      Raf oncogene (Raf) encodes a serine-threonine protein kinase that acts downstream of the product of Ras85D. It activates the MEK/ERK pathway to regulate cell proliferation, differentiation and survival downstream of receptor tyrosine kinases such as those encoded by tor, Egfr, and sev. [Date last reviewed: 2019-03-14]
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human RAF1, BRAF, and ARAF (1 Drosophila to 3 human); Dmel\Raf shares 43-47% identity and 56-60% 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
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (105 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        proximity ligation assay, fluorescence microscopy
        colocalization, fluorescence microscopy, inferred by author, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, proximity-dependent biotin identification, proximity ligation assay
        proximity ligation assay, fluorescence microscopy
        anti bait coimmunoprecipitation, western blot, isothermal titration calorimetry, predetermined participant, x-ray crystallography
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, western blot, pull down
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, autoradiography
        anti tag coimmunoprecipitation, western blot
        pull down, autoradiography, two hybrid, anti tag coimmunoprecipitation, anti tag western blot
        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
        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 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, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        enzymatic study, autoradiography
        two hybrid, anti tag coimmunoprecipitation, western blot, peptide massfingerprinting
        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, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot, 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, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, 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, 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 western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, peptide massfingerprinting
        anti tag coimmunoprecipitation, anti tag western blot, two hybrid
        pull down, two hybrid, anti tag coimmunoprecipitation, 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, 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, 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, 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
        Alleles Reported to Model Human Disease (Disease Ontology) (23 alleles)
        Models Based on Experimental Evidence ( 10 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 11 )
        Allele
        Disease
        Interaction
        References
        model of  carcinoma
        is ameliorated by CtBPHMS00677
        is ameliorated by CtBPJF01291
        is ameliorated by pucUAS.cMa
        model of  cancer
        model of  cancer
        model of  carcinoma
        is ameliorated by licGD7546
        is ameliorated by licJF01433
        is ameliorated by panJF02306
        is ameliorated by wgGD5007
        is ameliorated by Toll-7GD14417
        is ameliorated by Toll-7HM05230
        model of  carcinoma
        is exacerbated by Rho172F
        is exacerbated by RokGD1522
        is exacerbated by Toll-6GD14438
        is exacerbated by Toll-6GD35
        is exacerbated by kstGLC01654
        is exacerbated by sqhGL00663
        is exacerbated by zipGD1566
        is exacerbated by DefSK3
        is exacerbated by egr3
        is exacerbated by bskDN.UAS.cUa
        is ameliorated by msnUAS.cSa
        is ameliorated by Diap1UAS.cHa
        is ameliorated by Ire1GD3071
        is ameliorated by Ire1f02170
        is ameliorated by Xbp1GD4745
        is exacerbated by bskDN.UAS
        model of  cancer
        is ameliorated by hepr75
        is ameliorated by ykiB5
        is ameliorated by egr1
        is ameliorated by Ilp21
        is exacerbated by Ilp2UAS.cBa
        is ameliorated by Ilp53
        is exacerbated by InRUAS.Exel
        is exacerbated by chico1
        model of  carcinoma
        is exacerbated by aptGD1367
        is ameliorated by aptUAS.cEa
        is ameliorated by Gadd45KK104250
        is ameliorated by GlyatTH00482
        is ameliorated by Glyatc02982
        is ameliorated by Gadd45HMS01436
        Models Based on Experimental Evidence ( 5 )
        Modifiers Based on Experimental Evidence ( 9 )
        Allele
        Disease
        Interaction
        References
        model of  cancer
        is ameliorated by slifUY681
        is ameliorated by Atg1HMS02750
        is exacerbated by Atg1016h
        is ameliorated by Atg16MI00187
        is ameliorated by Atg5HMS01244
        is ameliorated by Atg6HMS01483
        is ameliorated by BalatHMC06377
        is ameliorated by CarTHMC04919
        is ameliorated by CatUAS.cAa
        is ameliorated by bskHMS00777
        is ameliorated by bskK53R.UAS
        is ameliorated by slifHMC05846
        ameliorates  Huntington's disease
        modeled by @Huntington's??not a valid allele symbol??@, @disease??not a valid allele symbol??@
        is ameliorated by sloHMC04093
        is ameliorated by sloJF02146
        is ameliorated by sloKO
        is exacerbated by sloUAS.cXa
        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
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        nitrosomethyl urea
        loss of function allele
        amorphic allele - genetic evidence
        X ray
        amorphic allele - genetic evidence
        1,2-dichloroethane
        amorphic allele - genetic evidence
        spontaneous
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        hycanthon methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        X ray
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        References (8)