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Nutrient restriction enhances the proliferative potential of cells lacking the tumor suppressor PTEN in mitotic

Katarzyna Nowak1, Gerhard Seisenbacher, Ernst Hafen

  • 1Institute of Molecular Systems Biology , ETH Zürich , Zürich , Switzerland.

Elife
|July 16, 2013
PubMed

Insights

Cancer hallmarks in single cells are unclear. Lacking the PTEN tumor suppressor, cells overproliferate in nutrient-restricted Drosophila, driven by PI3K/Akt/TORC1 signaling, revealing how diet impacts cancer development.

Area of Science:

  • Developmental Biology
  • Cancer Biology
  • Cell Signaling

Background:

  • The acquisition of cancer hallmarks by single cells in developing tissues remains poorly understood.
  • PTEN (phosphatase and tensin homolog) is a critical tumor suppressor regulating PI3K signaling.
  • Nutritional status is known to influence cellular growth and metabolism.

Purpose of the Study:

  • To investigate how loss of the PTEN tumor suppressor affects cell behavior in Drosophila imaginal tissues under varying nutritional conditions.
  • To elucidate the signaling pathways and mechanisms driving hyperplastic overgrowth in PTEN-deficient cells.

Main Methods:

  • Utilized mitotic recombination in Drosophila imaginal discs to generate PTEN-null clones.
  • Manipulated nutritional conditions (nutrient restriction) in larval stages.
  • Analyzed cell proliferation, survival, and signaling pathway activity (Akt/PKB, TORC1, amino acid transporters).

Main Results:

  • PTEN-deficient cells exhibited significant overproliferation specifically under nutrient-restricted conditions.
  • Overgrowth was dependent on PI3K/Akt/TORC1 pathway activation.
  • Reduced amino acid uptake via Slimfast transporter led to the collapse of PTEN-mutant cell clones.
  • PTEN mutant cells employed mechanisms distinct from cell competition to outcompete neighbors.

Conclusions:

  • Limiting nutritional conditions exacerbate the effects of PTEN loss, leading to hyperplastic overgrowth.
  • The PI3K/Akt/TORC1 pathway and amino acid transport are crucial for the survival and proliferation of PTEN-deficient cells.
  • This study provides insights into how nutrient availability can modulate tumor development initiated by PTEN loss.
Keywords:
D. melanogasterPTENapoptosishyperplasiainsulin signalingnutrient restrictiontumor suppression

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