FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: cancer, epithelial, Par-complex-related
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General Information
Name
cancer, epithelial, Par-complex-related
FlyBase ID
FBhh0000810
Disease Ontology Term
Parent Disease
OMIM
Overview

Loss of apical-basal polarity is an early event in the development of epithelial cancers. Epithelial cell polarity is maintained by three highly conserved polarity complexes, Par, Crumbs (CRB) and Scribble (SCRIB). In Drosophila, the Par complex consists of Dmel\baz (PARD3, PARD3B in human), Dmel\Cdc42 (CDC42 in human), Dmel\par-6 (PARD6A, PARD6B, PARD6G in human) and Dmel\aPKC (PRKCI, PRKCZ in human). This complex is variously called the PAR3-aPKC-PAR6 complex, the Cdc42-Par6-aPKC complex, the aPKC-PAR complex, or other combinations of the components; the junctional apical-basal polarity complex or the junctional ABP complex. The four component fly genes have been extensively studied: classical loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for each; physical and genetic interactions have been described for each; see below and in the respective gene reports.

The human Hsap\CDC42 and Hsap\PARD6B genes have been introduced into flies, but have not been characterized in context of this disease model.

Assayed in imaginal discs in flies, loss-of-function mutations of the Par complex genes exhibit polarity and other epithelial defects, but do not result in overgrowth phenotypes. Early work in Drosophila demonstrated that loss-of-function mutations of baz or Cdc42, in combination with a Ras85D activated mutation, transform the activated Ras overproliferation phenotype into an invasive phenotype.

Drosophila larval wing imaginal discs undergo apoptosis-induced compensatory proliferation following tissue injury; this can be assayed by exposing larvae to irradiation. Loss of Cdc42, and to a lesser extent aPKC, increase this proliferation response. Cdc42, baz, aPKC, and par-6 have been characterized in combination with the anti-apoptotic p35 gene from baculovirus (BacA\p35). When apoptosis is blocked by p35 expression, Par-complex-depleted tissues are hyperproliferative, leading to tissue and organ overgrowth.

Activated aPKC expressed in wing discs has been used in transplantation assays; hosts develop malignant tumors. Reduced lifespan is observed, in part due to impact on the blood-brain barrier. Data suggest that transplanted tumors actively induce blood-brain barrier permeabilization; preventing the increased blood-brain barrier permeabilization extends the host lifespan.

[updated Oct. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, epithelial, Par-complex-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
    Disease synonyms
    Search term: aPKC/Par3/Par6 complex
    Search term: aPKC-PAR complex
    Search term: Cdc42-Par6-aPKC complex
    Search term: junctional ABP complex
    Search term: junctional apical-basal polarity complex
    Search term: Par3/Par6/aPKC complex
    Search term: PAR3-aPKC-PAR6 complex
    Search term: Partitioning-defective complex
    Ortholog Information
    Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (4)
      Gene Snapshot
      bazooka (baz) encodes a scaffold protein that forms a complex with the products of par-6 and aPKC and with other cortical, cytoskeletal and regulatory proteins. It functions in cell polarization pathways in epithelial, neuronal and other cell types. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate- to high-scoring ortholog of human PARD3 and PARD3B (1 Drosophila to 2 human). Dmel\baz shares 22-26% identity and 34-38% 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
      Cell division cycle 42 (Cdc42) encodes a GTPase signaling protein that acts as a molecular switch and functions as key regulator of the actin cytoskeleton. It plays a central role in diverse biological processes including actin cytoskeleton organization, morphogenesis, hemocyte migration, cell polarity, and wound repair. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human CDC42 (1 Drosophila to 1 human). Dmel\Cdc42 shares 92% identity and 95% similarity with the human gene.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      atypical protein kinase C (aPKC) encodes a member of the conserved Par complex and is asymmetrically localized to the apical cortex, where it phosphorylates and thus excludes the basal determinants encoded by mira and numb. It is involved in neuroblast proliferation and self-renewal. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Moderate- to high-scoring ortholog of human PRKCI and PRKCZ (1 Drosophila to 2 human). Dmel\aPKC shares 60-63% identity and 70-74% 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
      par-6 (par-6) encodes a scaffold protein that forms a complex with the products of baz and aPKC and with other cortical, cytoskeletal and regulatory proteins. It is involved in cell polarization, actin-based protrusion formation and tracheal branching. [Date last reviewed: 2019-06-13]
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human PARD6A, PARD6B, and PARD6G (1 Drosophila to 3 human). Dmel\par-6 shares 48-55% identity and 62-73% 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 (116 groups)
        protein-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, western blot, anti tag western blot, two hybrid, pull down, autoradiography, cross-linking study
        anti tag coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, western blot
        protein kinase assay, autoradiography, two hybrid, pull down, western blot, anti tag coimmunoprecipitation, anti bait coimmunoprecipitation, molecular weight estimation by staining, anti tag western blot
        two hybrid, anti bait coimmunoprecipitation, western blot, pull down, autoradiography
        anti tag coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, western blot
        pull down, autoradiography
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        two hybrid, pull down, autoradiography, anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot, western blot
        anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, pull down, autoradiography
        anti bait coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, anti tag western blot
        anti bait coimmunoprecipitation, Identification by mass spectrometry, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, western blot
        pull down, western blot, nuclear magnetic resonance, anti tag western blot, anti bait coimmunoprecipitation, molecular weight estimation by staining, autoradiography, x-ray crystallography
        anti bait coimmunoprecipitation, western blot
        pull down, anti tag western blot
        anti bait coimmunoprecipitation, anti tag western blot, western blot, two hybrid
        anti tag coimmunoprecipitation, anti tag western blot, two hybrid
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot, pull down
        anti bait coimmunoprecipitation, western blot, nuclear magnetic resonance
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, western blot, two hybrid, nuclear magnetic resonance, predetermined participant
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, western blot
        pull down, autoradiography, anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, western blot
        protein-protein
        Interacting group
        Assay
        References
        pull down, western blot
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        pull down, anti tag western blot, western blot, two hybrid, autoradiography
        anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
        pull down, autoradiography
        pull down, autoradiography, enzymatic study
        two hybrid, pull down, autoradiography
        pull down, anti tag western blot, western blot, anti tag coimmunoprecipitation
        pull down, autoradiography, western blot
        anti tag coimmunoprecipitation, western blot
        pull down, molecular weight estimation by coomasie staining, western blot, autoradiography, nuclear magnetic resonance
        pull down, anti tag western blot, autoradiography
        anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, anti tag western blot, enzymatic study, fluorescence technology
        pull down, autoradiography
        pull down, western blot
        pull down, autoradiography
        pull down, autoradiography, anti tag coimmunoprecipitation, western blot
        pull down, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting
        pull down, western blot, autoradiography, anti tag western blot, enzymatic study, fluorescent resonance energy transfer, fluorescence microscopy
        pull down, anti tag western blot, autoradiography
        RNA-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, quantitative reverse transcription pcr
        RNA-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, reverse transcription pcr
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        pull down, western blot, electrophoretic mobility shift assay, autoradiography, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        protein-protein
        Interacting group
        Assay
        References
        enzymatic study, autoradiography
        enzymatic study, autoradiography
        protein kinase assay, autoradiography, two hybrid, pull down, western blot, anti tag coimmunoprecipitation, anti bait coimmunoprecipitation, molecular weight estimation by staining, anti tag western blot
        anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        phenotype-based detection assay, fluorescence microscopy, inferred by author, pull down, western blot, anti tag western blot
        anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry, pull down, autoradiography
        enzymatic study, Identification by mass spectrometry
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot, experimental knowledge based, proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, peptide massfingerprinting
        proximity ligation assay, fluorescence microscopy, anti bait coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot, enzymatic study, autoradiography, pull down, anti tag coimmunoprecipitation, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot
        two hybrid, pull down, autoradiography
        pull down, western blot, protein kinase assay, autoradiography, anti tag coimmunoprecipitation, peptide massfingerprinting
        pull down, western blot
        anti tag coimmunoprecipitation, peptide massfingerprinting, western blot
        two hybrid, anti tag coimmunoprecipitation, western blot, pull down, autoradiography, peptide massfingerprinting, anti bait coimmunoprecipitation, anti tag western blot, experimental knowledge based
        pull down, western blot, anti tag western blot
        anti tag coimmunoprecipitation, western blot
        pull down, western blot
        anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation
        anti tag coimmunoprecipitation, anti tag western blot
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        anti bait coimmunoprecipitation, western blot
        enzymatic study, autoradiography, peptide massfingerprinting, anti bait coimmunoprecipitation, western blot, pull down
        RNA-protein
        Interacting group
        Assay
        References
        anti tag coimmunoprecipitation, primer specific pcr
        anti bait coimmunoprecipitation, quantitative reverse transcription pcr
        anti bait coimmunoprecipitation, primer specific pcr
        RNA-RNA
        Interacting group
        Assay
        References
        protein-protein
        Interacting group
        Assay
        References
        two hybrid, anti tag coimmunoprecipitation, western blot, pull down, autoradiography, peptide massfingerprinting, anti bait coimmunoprecipitation, anti tag western blot, experimental knowledge based
        enzymatic study, autoradiography
        pull down, western blot, nuclear magnetic resonance, anti tag western blot, anti bait coimmunoprecipitation, molecular weight estimation by staining, autoradiography, x-ray crystallography
        pull down, molecular weight estimation by coomasie staining, western blot, autoradiography, nuclear magnetic resonance
        nuclear magnetic resonance, pull down, western blot, anti tag coimmunoprecipitation, two hybrid, x-ray crystallography, phenotype-based detection assay, fluorescence microscopy, inferred by author
        pull down, autoradiography
        anti bait coimmunoprecipitation, western blot, anti tag western blot, peptide massfingerprinting, experimental knowledge based, pull down, autoradiography, anti tag coimmunoprecipitation
        pull down, western blot
        anti tag coimmunoprecipitation, anti tag western blot
        pull down, western blot
        pull down, western blot, anti tag western blot
        anti tag coimmunoprecipitation, anti tag western blot, pull down
        pull down, western blot
        anti tag coimmunoprecipitation, western blot
        pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, two hybrid, peptide massfingerprinting
        protein-protein
        Interacting group
        Assay
        References
        enzymatic study, fluorescence technology
        Alleles Reported to Model Human Disease (Disease Ontology) (11 alleles)
        Models Based on Experimental Evidence ( 2 )
        Modifiers Based on Experimental Evidence ( 2 )
        Allele
        Disease
        Interaction
        References
        Models Based on Experimental Evidence ( 3 )
        Modifiers Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Interaction
        References
        Models Based on Experimental Evidence ( 3 )
        Modifiers Based on Experimental Evidence ( 3 )
        Allele
        Disease
        Interaction
        References
        model of  cancer
        is NOT ameliorated by bskK53R.UAS
        Models Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Evidence
        References
        Modifiers Based on Experimental Evidence ( 1 )
        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
        ethyl methanesulfonate
        amorphic allele - genetic evidence
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        loss of function allele
        ethyl methanesulfonate
        ethyl methanesulfonate
        amorphic allele - molecular evidence
        CRISPR/Cas9
        References (22)