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The Drosophila Imaginal Disc Tumor Model: Visualization and Quantification of Gene Expression and Tumor Invasiveness Using Genetic Mosaics
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dTcf/Pangolin suppresses growth and tumor formation in Drosophila

Shilin Song1, Diana Andrejeva1, Flávia C P Freitas1

  • 1Department of Cellular and Molecular Medicine, University of Copenhagen, 2200N Copenhagen, Denmark.

Proceedings of the National Academy of Sciences of the United States of America
|June 26, 2019
PubMed

Insights

The transcription factor dTcf/Pangolin (Pan) limits tissue growth and suppresses tumor development in Drosophila. It acts as a repressor of normal and oncogenic growth, identifying Sox15 and Ftz-f1 as key downstream genes.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Wnt/Wingless (Wg) signaling is crucial for animal development and implicated in human cancers.
  • dTcf/Pangolin (Pan) is the key effector of the Wg pathway, acting as a dual regulator of target gene expression.
  • In the absence of Wg, dTcf/Pan functions as a transcriptional repressor, partnering with TLE/Groucho (Gro).

Purpose of the Study:

  • To investigate the role of dTcf/Pangolin (Pan) in growth control and tumorigenesis within the proliferating epithelium of the Drosophila wing imaginal disk.
  • To elucidate the function of dTcf/Pan in regulating normal tissue growth and its impact on oncogene-induced tumor development.
  • To identify downstream genes regulated by dTcf/Pan that are involved in tumor formation.

Main Methods:

  • Utilized the Drosophila wing imaginal disk as a model system to study epithelial proliferation.
  • Analyzed the function of dTcf/Pangolin (Pan) in both normal development and oncogenic contexts.
  • Employed genetic and molecular techniques to identify genes regulated by dTcf/Pan.

Main Results:

  • dTcf/Pangolin (Pan) was found to limit tissue growth during normal Drosophila development.
  • dTcf/Pangolin (Pan) demonstrated a tumor-suppressive role, inhibiting tumorigenesis when oncogenes were upregulated.
  • The study identified Sox box protein 15 (Sox15) and Ftz transcription factor 1 (Ftz-f1) as dTcf/Pan-regulated genes critical for tumor development.

Conclusions:

  • dTcf/Pangolin (Pan) acts as a repressor of both normal and oncogenic growth in Drosophila.
  • The findings reveal a novel tumor-suppressive function for dTcf/Pangolin (Pan) in epithelial tissues.
  • Identified Sox15 and Ftz-f1 as key downstream targets of dTcf/Pangolin (Pan) mediating its role in tumorigenesis.
Keywords:
DrosophilaTCF/LEFWntcancergrowth control

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