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Updated: Aug 21, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

The human protein Hugl-1 substitutes for Drosophila lethal giant larvae tumour suppressor function in vivo

Daniela Grifoni1, Flavio Garoia, Christoph C Schimanski

  • 1Alma Mater Studiorum, Dipartimento di Biologia Evoluzionistica Sperimentale, Via Selmi 3, 40126 Bologna, Italy. dgrifoni@alma.unibo.it

Oncogene
|October 7, 2004
PubMed

Insights

The human homologue of the Drosophila tumor suppressor gene lethal giant larvae (lgl), Hugl-1, is lost in human cancers. Hugl-1 rescues lgl mutations in flies, confirming its tumor suppressor role and conserved function in mammals.

Area of Science:

  • Cell Biology
  • Genetics
  • Developmental Biology

Background:

  • Tumor suppressor genes lethal giant larvae (lgl), discs large (dlg), and scribble (scrib) are crucial for cell polarity and tissue architecture.
  • Disruption of these genes leads to uncontrolled cell proliferation and tumor formation.
  • Mammalian homologues of these genes are conserved and implicated in human tumorigenesis.

Purpose of the Study:

  • To investigate the functional conservation between Drosophila lgl and its human homologue, Hugl-1 (Llgl1).
  • To determine if Hugl-1 functions as a tumor suppressor in humans and can rescue lgl mutations in Drosophila.
  • To explore the conserved genetic pathway involving lgl, dlg, and scrib in mammals.

Main Methods:

  • Analysis of Hugl-1 expression in human solid malignancies.
  • Expression of human Hugl-1 in homozygous lgl Drosophila mutants.
  • Assessment of tumor suppression, tissue architecture, and protein localization (Dlg, Scrib) in rescued Drosophila.
  • Testing the ability of human scrib and mammalian dlg to rescue their respective Drosophila mutations.

Main Results:

  • Hugl-1 is frequently lost in human solid tumors, supporting its role as a tumor suppressor.
  • Hugl-1 expression rescues larval lethality in lgl Drosophila mutants.
  • Rescued Drosophila tissues exhibit normal architecture, correct Dlg and Scrib localization, and complete metamorphosis.
  • Human scrib and mammalian dlg also rescue their corresponding Drosophila mutations, indicating pathway conservation.

Conclusions:

  • Hugl-1 is the functional homologue of Drosophila lgl and acts as a tumor suppressor.
  • The tumor suppressor pathway involving lgl, dlg, and scrib is conserved in mammals.
  • Drosophila serves as a valuable model for studying the link between cell polarity loss and cancer in humans.

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