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A Behavioral Assay for Mechanosensation of MARCM-based Clones in Drosophila melanogaster
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Methionine restriction breaks obligatory coupling of cell proliferation and death by an oncogene Src in Drosophila

Hiroshi Nishida1,2, Morihiro Okada2,3, Lynna Yang2

  • 1Division of Cell Physiology, Kobe University, Kobe, Japan.

Elife
|April 27, 2021
PubMed

Insights

The oncogene Src drives cell proliferation and death via parallel MAPK pathways. Reducing dietary methionine uncouples these processes, suppressing tumor growth and lethality by exploiting a cellular fail-safe mechanism.

Area of Science:

  • Cellular Biology
  • Oncology
  • Molecular Biology

Background:

  • Oncogenes can paradoxically promote both cell proliferation and cell death.
  • Understanding the mechanisms by which oncogenes regulate these opposing cellular outcomes is crucial for cancer research.
  • It remains unclear whether oncogene-induced cell death is a consequence of aberrant proliferation or an independent process.

Purpose of the Study:

  • To elucidate how the oncogene Src simultaneously drives cell proliferation and death.
  • To investigate the role of parallel MAPK pathways in mediating these dual effects.
  • To explore the potential of dietary interventions in modulating oncogene-driven tumorigenesis.

Main Methods:

  • Utilized Src as the model oncogene.
  • Investigated parallel mitogen-activated protein kinase (MAPK) pathways, specifically p38 and JNK.
  • Examined the role of the protein Slpr as a divergence point for MAPK signaling.
  • Assessed the impact of methionine-mediated Tor signaling on proliferation.
  • Studied the effects of dietary methionine reduction on tumorigenesis and lethality.

Main Results:

  • Src simultaneously drives cell proliferation and death through an obligatorily coupled mechanism involving parallel MAPK pathways.
  • The p38 MAPK pathway promotes proliferation, while the JNK MAPK pathway induces apoptosis independently of proliferation signals.
  • Src-induced proliferation is regulated by methionine-dependent Tor signaling.
  • Reducing dietary methionine uncouples proliferation and death, thereby suppressing tumorigenesis and tumor-induced lethality.

Conclusions:

  • Src employs parallel MAPK pathways to orchestrate both proliferation and apoptosis, revealing a coupled mechanism.
  • Dietary methionine restriction offers a potential strategy to disrupt this coupling and counteract Src-driven oncogenesis.
  • The findings highlight an evolved cellular fail-safe mechanism against oncogene Src and suggest diet-based approaches to cancer prevention.
Keywords:
D. melanogastercancer biologycell deathmethioninenutritiononcogeneproliferation

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