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Updated: Jul 31, 2025

The Drosophila Imaginal Disc Tumor Model: Visualization and Quantification of Gene Expression and Tumor Invasiveness Using Genetic Mosaics
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Oncogenic stress-induced Netrin is a humoral signaling molecule that reprograms systemic metabolism in Drosophila

Morihiro Okada1,2, Tomomi Takano1,2, Yuko Ikegawa2,3

  • 1Physiological Genetics Laboratory, RIKEN CPR, Kobe, Japan.

The EMBO Journal
|May 4, 2023
PubMed

Insights

Cancerous cells release NetrinB (NetB), a protein that disrupts systemic metabolism and causes organismal death. Suppressing NetB or its receptor prevents death by restoring metabolic function and carnitine biosynthesis.

Area of Science:

  • Molecular Biology
  • Metabolic Research
  • Cancer Biology

Background:

  • Cancer causes systemic effects, leading to organismal death, but the mechanisms remain unclear.
  • NetrinB (NetB) is known as a tissue-level axon guidance cue.
  • The systemic role of NetB in cancer progression is unexplored.

Purpose of the Study:

  • To investigate the role of NetrinB (NetB) in mediating systemic effects of oncogenic stress.
  • To explore NetB's function as a humoral factor in cancer-induced metabolic reprogramming.
  • To identify therapeutic targets for mitigating cancer's systemic impact.

Main Methods:

  • Utilized Drosophila models with Ras-induced dysplastic cells.
  • Assessed the impact of inhibiting NetB or its receptor in the fat body.
  • Measured carnitine biosynthesis and acetyl-CoA generation.
  • Supplemented with carnitine or acetyl-CoA to evaluate amelioration of organismal health.

Main Results:

  • Ras-induced dysplastic cells upregulate and secrete NetB.
  • Inhibiting NetB or its receptor in the fat body suppressed oncogenic stress-induced organismal death.
  • NetB remotely suppressed carnitine biosynthesis in the fat body, impacting acetyl-CoA generation.
  • Carnitine or acetyl-CoA supplementation ameliorated organismal health under oncogenic stress.

Conclusions:

  • NetrinB (NetB) acts as a humoral factor in mediating systemic effects of oncogenic stress.
  • NetB disrupts organismal metabolism by suppressing carnitine biosynthesis.
  • Targeting NetB or its downstream metabolic pathways offers potential therapeutic strategies against cancer's systemic effects.
Keywords:
DrosophilaNetrininter-organ communicationoncogenic stress

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