FB2026_02 , released June 18, 2026
Human Disease Model Report: cancer, multiple, actin-remodeling regulators
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General Information
Name
cancer, multiple, actin-remodeling regulators
FlyBase ID
FBhh0001148
Disease Ontology Term
Parent Disease
OMIM
Overview

Regulators of actin and cytoskeletal remodeling play a key role in orchestrating the cytoskeletal changes required for cell migration, in both normal and pathogenic contexts. Evidence is accumulating that, in addition to this function, actin remodeling regulators may participate in positive feedback networks that impact development of malignant phenotypes during the early stages of cellular transformation. Studies in Drosophila have contributed to understanding of these interactions.

Several slightly different models have been used; most use assays in wing discs with overexpression of Src64B or knockdown of Csk in discrete regions of the disc. Dmel\Src64B is the highest-scoring Drosophila ortholog of human gene SRC. Dmel\Csk is orthologous to the human CSK gene, a kinase that suppresses the activity of multiple genes, including the SRC proto-oncogene. Interacting genes were identified and characterized based on changes in the Src-related overproliferation phenotypes.

Actin modulators that have emerged as important in this process include ena (orthologous to human ENAH, EVL and VASP); tsr (orthologous to human CFL2, DSTN and CFL1); cpa (orthologous to human CAPZA1, CAPZA2 and CAPZA3); and cpb (orthologous to human CAPZB). A large-scale genetic screen has identified additional candidates.

The impact of overexpression of Dmel\ena has also been characterized in migrating embryonic macrophages (hemocytes) to address development of aggressive migratory behavior during cancer progression.

[updated Feb. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, multiple, actin-remodeling regulators
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
    Disease synonyms
    cancer, epithelial, actin-remodeling regulators
    cancer, epithelial, SRC with actin-remodeling regulators
    Ortholog Information
    Human gene(s) in FlyBase
      Other mammalian ortholog(s) used
        D. melanogaster Gene Information (6)
        Gene Snapshot
        Src oncogene at 64B (Src64B) encodes a Src family nonreceptor tyrosine kinase. It has many biological roles, including ring canal morphogenesis in oogenesis and the male germline, microfilament ring constriction during cellularization, and modulation of growth and apoptosis. Some of its roles overlap with those of the product of Src42A. [Date last reviewed: 2019-03-14]
        Gene Groups / Pathways
        Comments on ortholog(s)

        Highest-scoring ortholog of human gene SRC (many to many; multiple paralogs and orthologs in both species). Dmel\Src64B shares 50% identity and 67% similarity with human SRC.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Gene Snapshot
        C-terminal Src kinase (Csk) encodes a cytoplasmic tyrosine kinase that acts as a tumor suppressor through Src pathway inibition as well as a mediator of the activity of the product of Egfr. [Date last reviewed: 2019-03-07]
        Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        High-scoring ortholog of human CSK; moderate-scoring ortholog of human MATK (1 Drosophila to 2 human); Dmel\Csk shares 62% identity and 75% similarity with the human CSK gene.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Gene Snapshot
        enabled (ena) encodes the sole Drosophila member of the Ena/VASP family. It acts as a processive actin polymerase, stimulating actin addition at the barbed end. It has roles in both epithelial morphogenesis and CNS pathfinding. [Date last reviewed: 2019-03-07]
        Molecular function (GO)
        Gene Groups / Pathways
          Comments on ortholog(s)

          Moderate-scoring ortholog of human ENAH, EVL and VASP.

          Orthologs and Alignments from DRSC
          DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
          Molecular function (GO)
          Gene Groups / Pathways
            Comments on ortholog(s)

            Moderate-scoring ortholog of human CFL2, DSTN and CFL1.

            Orthologs and Alignments from DRSC
            DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
            Gene Snapshot
            capping protein beta (cpb) encodes an actin-binding protein that, together with cpa, binds to the fast growing ends of actin filaments, restricting the addition or loss of actin monomers. It restricts JNK signaling, modulates Hippo signaling, maintains epithelial integrity and neuronal homeostasis, controls proliferation/apoptosis in wing imaginal discs, and promotes oogenesis. [Date last reviewed: 2018-09-13]
            Gene Groups / Pathways
            Comments on ortholog(s)

            High-scoring ortholog of human CAPZB.

            Orthologs and Alignments from DRSC
            DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
            Gene Snapshot
            capping protein alpha (cpa) encodes an actin-binding protein that, along with the product of cpb, binds to the fast growing ends of actin filaments to restrict the addition or loss of actin monomers. It limits the nuclear translocation of the Hippo pathway mediator encoded by yki and restricts JNK signaling. It maintains epithelial integrity and controls the balance between proliferation and apoptosis in the wing imaginal disc. It plays important roles during oogenesis, as well as maintaining neuronal homeostasis. [Date last reviewed: 2018-10-18]
            Gene Groups / Pathways
            Comments on ortholog(s)

            Moderate- to high-scoring ortholog of human CAPZA1, CAPZA2 and CAPZA3.

            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 (91 groups)
              protein-protein
              Interacting group
              Assay
              References
              enzymatic study, autoradiography
              anti tag coimmunoprecipitation, anti tag western blot
              pull down, anti tag western blot, two hybrid
              pull down, anti tag western blot
              enzymatic study, autoradiography
              two hybrid, anti tag coimmunoprecipitation, anti tag western blot
              anti tag coimmunoprecipitation, multidimensional protein identification technology, western blot
              anti tag coimmunoprecipitation, western blot
              anti bait coimmunoprecipitation, anti tag western blot
              anti tag coimmunoprecipitation, anti tag western blot
              protein-protein
              Interacting group
              Assay
              References
              pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot
              proximity ligation assay, fluorescence microscopy
              enzymatic study, western blot, autoradiography
              enzymatic study, autoradiography
              enzymatic study, western blot
              protein-protein
              Interacting group
              Assay
              References
              anti tag coimmunoprecipitation, anti tag western blot, two hybrid
              pull down, anti tag western blot, western blot, far western blotting, peptide array
              enzymatic study, autoradiography, pull down, western blot, far western blotting, anti tag western blot, peptide massfingerprinting
              two hybrid, anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot
              anti tag coimmunoprecipitation, anti tag western blot
              bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, western blot, pull down, two hybrid
              pull down, western blot
              anti tag coimmunoprecipitation, peptide massfingerprinting
              two hybrid, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot
              anti tag coimmunoprecipitation, western blot, pull down, enzymatic study, autoradiography
              two hybrid, anti tag coimmunoprecipitation, western blot
              pull down, western blot
              pull down, western blot
              pull down, western blot, anti bait coimmunoprecipitation, autoradiography, anti tag coimmunoprecipitation
              experimental knowledge based
              pull down, western blot
              anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, autoradiography
              RNA-RNA
              Interacting group
              Assay
              References
              immunohistochemistry, fluorescence technology, necessary binding region
              protein-protein
              Interacting group
              Assay
              References
              experimental knowledge based
              anti tag coimmunoprecipitation, western blot
              experimental knowledge based
              enzymatic study, autoradiography
              anti tag coimmunoprecipitation, western blot, pull down, Identification by mass spectrometry
              anti tag coimmunoprecipitation, western blot
              anti tag coimmunoprecipitation, western blot
              anti tag coimmunoprecipitation, comigration in sds page, anti tag western blot
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              anti tag coimmunoprecipitation, western blot, bimolecular fluorescence complementation, fluorescence microscopy, proximity ligation assay
              RNA-protein
              Interacting group
              Assay
              References
              anti tag coimmunoprecipitation, partial DNA sequence identification by hybridization, anti bait coimmunoprecipitation
              protein-protein
              Interacting group
              Assay
              References
              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
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              anti bait coimmunoprecipitation, western blot, peptide massfingerprinting
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              anti tag coimmunoprecipitation, peptide massfingerprinting
              experimental knowledge based
              anti tag coimmunoprecipitation, Identification by mass spectrometry
              anti tag coimmunoprecipitation, Identification by mass spectrometry
              experimental knowledge based
              protein-protein
              Interacting group
              Assay
              References
              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
              experimental knowledge based
              anti bait coimmunoprecipitation, peptide massfingerprinting
              experimental knowledge based
              experimental knowledge based
              experimental knowledge based
              anti tag coimmunoprecipitation, peptide massfingerprinting
              anti tag coimmunoprecipitation, peptide massfingerprinting
              experimental knowledge based
              anti tag coimmunoprecipitation, peptide massfingerprinting
              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
              Alleles Reported to Model Human Disease (Disease Ontology) (32 alleles)
              Models Based on Experimental Evidence ( 4 )
              Modifiers Based on Experimental Evidence ( 8 )
              Allele
              Disease
              Interaction
              References
              Models Based on Experimental Evidence ( 2 )
              Modifiers Based on Experimental Evidence ( 4 )
              Models Based on Experimental Evidence ( 0 )
              Allele
              Disease
              Evidence
              References
              Modifiers Based on Experimental Evidence ( 6 )
              Models Based on Experimental Evidence ( 7 )
              Modifiers Based on Experimental Evidence ( 7 )
              Models Based on Experimental Evidence ( 2 )
              Modifiers Based on Experimental Evidence ( 0 )
              Allele
              Disease
              Interaction
              References
              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
              ethyl methanesulfonate
              ethyl methanesulfonate
              loss of function allele
              P-element activity
              loss of function allele
              P-element activity
              loss of function allele
              amorphic allele - molecular evidence
              CRISPR/Cas9
              amorphic allele - molecular evidence
              CRISPR/Cas9
              amorphic allele - genetic evidence
              ethyl methanesulfonate
              amorphic allele - molecular evidence
              ethyl methanesulfonate
              loss of function allele
              Delta2-3 transposase
              loss of function allele
              Delta2-3 transposase
              ethyl methanesulfonate
              amorphic allele - genetic evidence
              ends-out gene targeting
              amorphic allele - molecular evidence
              CRISPR/Cas9
              ethyl methanesulfonate
              ethyl methanesulfonate
              References (6)