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General Information
Name
cancer, epithelial, LLGL-related
FlyBase ID
FBhh0000591
Disease Ontology Term
Parent Disease
OMIM
Overview

Loss of apical-basal polarity is an early event in the development of epithelial cancers. This model uses the Drosophila gene l(2)gl, which encodes a component of the Scribble polarity complex; this complex plays a key role in determining cell polarity and cell proliferation in epithelial cells. In human, there are two genes orthologous to Dmel\l(2)gl, the cytoskeletal proteins LLGL1 and LLGL2. Classical amorphic and hypomorphic mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\l(2)gl.

See also human diseases model reports 'cancer, epithelial, Scribble-complex-related' (FBhh0000586), 'cancer, epithelial, RAS-LLGL-related' (FBhh0000588), and 'cancer, epithelial, LLGL-YAP1-related' (FBhh0000590).

A tagged wild-type transgene of human Hsap\LLGL1 has been introduced into flies; partial heterologous rescue (functional complementation) of the homozygous Dmel\l(2)gl lethal phenotype is observed.

Animals homozygous for loss-of-function mutations of Dmel\l(2)gl typically die during the larval stage and exhibit abnormal overproliferation of tissues, including in the brain, imaginal discs, and hematopoietic organs; cell-polarity defects are observed. Somatic clones in different regions of the wing disc differ in susceptibility to development of l(2)gl-induced overproliferation: in some regions mutant cells are eliminated from mosaic epithelia by cell competition, in other regions clones produce tumor-like overgrowths. Observing that a number of microRNAs are dysregulated in l(2)gl tumors, a specific microRNA (mir-9a) was tested phenotypically; overexpression of mir-9a was found to reduce the overgrowth phenotype caused by loss of l(2)gl function in the wing epithelium. Multiple physical and many genetic interactions for Dmel\l(2)gl have been described; see below and in the gene report for l(2)gl.

[updated Jan. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, epithelial, LLGL-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
LLGL1 and LLGL2 encode cortical cytoskeleton proteins found in a complex involved in maintaining cell polarity and epithelial integrity, the Scribble Cell Polarity Complex. This complex plays a role in the initial phase of the establishment of epithelial cell polarity; it is involved in the regulation of mitotic spindle orientation, proliferation, differentiation, and tissue organization of neuroepithelial cells. [Gene Cards, LLGL1, LLGL2; 2017.08.01]
External links
Disease synonyms
Search term: neoplastic phenotype(s)
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)
Many to one: 2 human to 1 Drosophila; the second human gene is LLGL1.
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)
Many to one: 2 human to 1 Drosophila; the second human gene is LLGL2.
Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    lethal (2) giant larvae (l(2)gl) encodes a tumor suppressor protein that regulates cell polarity and asymmetric cell division. It acts on the basolateral side of epithelial cells, antagonizing the activity of apical complex proteins encoded by baz, par-6 and aPKC. [Date last reviewed: 2019-09-26]
    Gene Groups / Pathways
    Comments on ortholog(s)
    Moderate- to high-scoring ortholog of human LLGL1 and LLGL2 (1 Drosophila to 2 human). Dmel\l(2)gl shares 34-36% identity and 51-54% 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 (12 groups)
    protein-protein
    Interacting group
    Assay
    References
    anti tag coimmunoprecipitation, anti tag western blot
    anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based
    anti tag coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, anti tag western blot
    anti tag coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, western blot
    anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation
    anti bait coimmunoprecipitation, western blot, experimental knowledge based, pull down, autoradiography, anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
    proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot, pull down, Identification by mass spectrometry
    anti tag coimmunoprecipitation, anti tag western blot
    anti tag coimmunoprecipitation, anti tag western blot
    Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)
    Models Based on Experimental Evidence ( 3 )
    Modifiers Based on Experimental Evidence ( 1 )
    Allele
    Disease
    Interaction
    References
    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
    loss of function allele
    natural population
    amorphic allele - genetic evidence
    spontaneous
    amorphic allele - molecular evidence
    ends-out gene targeting
    References (30)