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Related Experiment Videos

Glycolytic enzymes can modulate cellular life span.

Hiroshi Kondoh1, Matilde E Lleonart, Jesus Gil

  • 1Wolfson Institute for Biomedical Research, University College London, London Research Institute, London, United Kingdom. hiroshi.kondoh@cancer.org.uk

Cancer Research
|January 25, 2005
PubMed
Summary

Researchers discovered that the glycolytic enzyme phosphoglycerate mutase (PGM) can immortalize cells. Increased PGM activity promotes cell proliferation and resistance to arrest, while its depletion causes senescence.

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Cancer Research

Background:

  • Cellular senescence is a state of irreversible growth arrest.
  • Understanding the molecular mechanisms of cellular immortalization is crucial for cancer research.

Purpose of the Study:

  • To identify genes involved in cellular immortalization.
  • To investigate the role of glycolysis in cell proliferation and senescence.

Main Methods:

  • Unbiased genetic screening in mouse embryonic fibroblasts.
  • Short interfering RNA (siRNA) for gene depletion.
  • Assays for glycolytic flux, proliferation, and senescence.

Main Results:

  • Phosphoglycerate mutase (PGM), a glycolytic enzyme, was identified as a gene that can immortalize cells.

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  • Increased PGM activity enhanced glycolytic flux, enabled indefinite proliferation, and conferred resistance to ras-induced arrest.
  • Depletion of PGM or glucosephosphate isomerase using siRNA triggered premature senescence.
  • Immortalized cells and embryonic stem cells showed higher glycolytic flux and oxidative damage resistance compared to senescent cells.
  • Wild-type p53 down-regulates PGM, suggesting p53 mutations facilitate immortalization by affecting PGM levels and glycolysis.
  • Conclusions:

    • Glycolytic enzymes, specifically PGM, play a significant role in cellular immortalization.
    • Modulating glycolytic flux is a potential strategy for controlling cell proliferation and senescence.
    • The p53 pathway interacts with glycolysis to regulate cell fate decisions, offering insights into cancer development.