FB2026_02 , released June 18, 2026
Human Disease Model Report: cancer, multiple, RAS with actin regulators
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General Information
Name
cancer, multiple, RAS with actin regulators
FlyBase ID
FBhh0001149
Disease Ontology Term
Parent Disease
OMIM
Overview

In Drosophila, clones or restricted sets of cells expressing the Ras85DV12 activated RAS mutation result in overproliferation, but typically do not produce neoplastic or metastatic phenotypes (see FBhh0000474). Multiple genes involved in regulation of actin dynamics were tested in combination with Ras85DV12, screening for exacerbation of the overproliferation phenotype.

The effects of combining overexpression of pico (ortholog of human RAPH1, aka Lamellipodin or LPD) with activated Ras85D (and with expression of a GFP label) were assessed in larval imaginal discs and optic lobes of the larval brain. Significant tissue overgrowth was observed and shown to be made up of GFP-positive cells; redistribution of cells to more distant sites was also observed, including from the brain to the ventral nerve cord. Invasive behavior was shown to be dependent upon JNK signaling. In the brain, it was shown that these effects are glial-specific and require glial co-expression of Ras85DV12 and pico.

Overexpression of the Drosophila gene that encodes profilin (chic), when assessed in these assays, results in similar phenotypes. For chic, also, the tumorigenic phenotypes require glial expression of both Ras85DV12 and chic. A loss-of-function allele of chic, when expressed in cells in addition to co-expression of Ras85DV12 and pico, reduces the level of invasive phenotypes.

[updated Nov. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, multiple, RAS with actin regulators
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

RAPH1 encodes a protein that belongs to the Mig10/Rap1-interacting adaptor molecule/Lamellipodin (MRL) family of adapter proteins, which function in cell migration. Members of this family contain pleckstrin-homology domains, Ras-association domains, and proline-rich C-termini. The protein encoded by this gene regulates actin dynamics through interaction with Ena/Vasodilator proteins as well as direct binding to filamentous actin to regulate actin network assembly. [Gene Cards, RAPH1; 2019.11.12]

Profilins are small actin-binding proteins found in eukaryotes and certain viruses that are involved in cell development, cytokinesis, membrane trafficking, and cell motility. Profilin is involved in actin polymerization dynamics and also interacts with polyphosphoinositides (PPI) and proline-rich domains containing proteins. Through its interaction with PPIs, profilin has been linked to signaling pathways between the cell membrane and the cytoskeleton, while its role in membrane trafficking has been associated with its interaction with proline-rich domain-containing proteins (Krishnan and Moens, 2009; pubmed:28509986).

External links
    Disease synonyms
    cancer, malignant glioma, RAS with actin regulators
    Ortholog Information
    Human gene(s) in FlyBase
      Other mammalian ortholog(s) used
        D. melanogaster Gene Information (3)
        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
        Gene Snapshot
        pico (pico) encodes an intracellular adapter protein belonging to the MRL family of proteins, which transduce signals from growth factor receptors to changes in the actin cytoskeleton. Its roles include the regulation of growth and cell migration. [Date last reviewed: 2019-03-14]
        Cellular component (GO)
        Gene Groups / Pathways
          Comments on ortholog(s)

          High-scoring ortholog of human RAPH1 (1 Drosophila to many human). Dmel\pico shares 26% identity and 39% similarity with human RAPH1.

          Orthologs and Alignments from DRSC
          DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
          Gene Snapshot
          chickadee (chic) encodes an actin monomer binding protein that provides the major cellular pool of readily polymerizing ATP-actin monomers. It is involved in oogenesis, spermatogenesis, cell division, bristle formation, cellular morphogenesis, axon growth, filopodia formation, dorsal closure, wound healing and stem cell maintenance. [Date last reviewed: 2019-03-07]
          Gene Groups / Pathways
            Comments on ortholog(s)

            High-scoring ortholog of human PFN4 (1 Drosophila to 4 human). Dmel\chic shares 28% identity and 42% similarity with human PFN4.

            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 (87 groups)
              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
              anti tag coimmunoprecipitation, autoradiography, two hybrid
              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
              pull down, western blot, two hybrid
              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
              pull down, covalent binding, western blot, anti tag coimmunoprecipitation, Identification by mass spectrometry
              protein-protein
              Interacting group
              Assay
              References
              anti tag coimmunoprecipitation, peptide massfingerprinting
              two hybrid, anti tag coimmunoprecipitation, western blot
              two hybrid, anti tag coimmunoprecipitation, anti tag western blot
              protein-protein
              Interacting group
              Assay
              References
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              anti tag coimmunoprecipitation, western blot, two hybrid, pull down, anti tag western blot
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based, anti bait coimmunoprecipitation, western blot
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              anti tag coimmunoprecipitation, anti tag western blot
              experimental knowledge based
              pull down, anti tag western blot
              anti tag coimmunoprecipitation, western blot
              experimental knowledge based
              two hybrid, anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              anti tag coimmunoprecipitation, peptide massfingerprinting
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
              experimental knowledge based
              anti tag coimmunoprecipitation, Identification by mass spectrometry
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              RNA-protein
              Interacting group
              Assay
              References
              anti tag coimmunoprecipitation, full identification by RNA sequencing, quantitative reverse transcription pcr, anti bait coimmunoprecipitation
              anti tag coimmunoprecipitation, quantitative reverse transcription pcr, proximity labelling technology, nucleotide sequence identification, reverse transcription pcr
              pull down, western blot, anti tag coimmunoprecipitation, quantitative reverse transcription pcr, electrophoretic mobility shift assay, autoradiography
              pull down, western blot
              proximity labelling technology, nucleotide sequence identification, anti tag coimmunoprecipitation, quantitative reverse transcription pcr
              Alleles Reported to Model Human Disease (Disease Ontology) (31 alleles)
              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 TimpUAS.cPa
              is ameliorated by bskDN.UAS
              is ameliorated by bskHMS00777
              is ameliorated by JraNIG.2275R
              is exacerbated by hepAct.UAS
              is exacerbated by imdUAS.cGa
              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 exacerbated by p53UAS.cUa
              is ameliorated by Ptip3804
              is ameliorated by Ilp8MI00727
              is exacerbated by Clbn1Q
              exacerbates  carcinoma
              model of  carcinoma
              is exacerbated by NkapGD11807
              Models Based on Experimental Evidence ( 0 )
              Allele
              Disease
              Evidence
              References
              Modifiers Based on Experimental Evidence ( 1 )
              Models Based on Experimental Evidence ( 2 )
              Allele
              Disease
              Evidence
              References
              Modifiers Based on Experimental Evidence ( 3 )
              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 - molecular evidence
              CRISPR/Cas9
              loss of function allele
              P-element activity
              amorphic allele - genetic evidence
              Delta2-3 transposase
              amorphic allele - genetic evidence
              Delta2-3 transposase
              loss of function allele
              loss of function allele
              P-element activity
              amorphic allele - genetic evidence
              References (3)