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Extracellular adenosine sensing-a metabolic cell death priming mechanism downstream of p53

Jaclyn S Long1, Diane Crighton, James O'Prey

  • 1Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.

Molecular Cell
|April 23, 2013
PubMed

Insights

The tumor suppressor p53 activates a cell death pathway sensing extracellular adenosine. This links cancer metabolism changes to cell death, enhancing tumor eradication.

Area of Science:

  • Cellular metabolism
  • Cancer biology
  • Molecular oncology

Background:

  • Tumor cells exhibit altered metabolism to support rapid growth.
  • Mechanisms linking metabolic changes to cancer cell death are crucial.
  • Extracellular adenosine levels increase with cellular stress and altered metabolism.

Purpose of the Study:

  • To investigate the role of the tumor suppressor p53 in sensing metabolic changes.
  • To identify pathways that link extracellular adenosine to cancer cell eradication.
  • To explore the function of adenosine receptor A2B in p53-mediated cell death.

Main Methods:

  • Analysis of p53-mediated upregulation of adenosine receptor A2B.
  • Assessment of A2B ligand engagement on cell viability.
  • Investigation of caspase- and Puma-dependent apoptotic pathways.
  • Evaluation of A2B stimulation in response to chemotherapeutic drugs and hypoxia.

Main Results:

  • p53 upregulates the expression of adenosine receptor A2B.
  • A2B activation triggers caspase- and Puma-dependent apoptosis.
  • Apoptotic response involves downregulation of antiapoptotic Bcl-2 proteins.
  • A2B stimulation enhances p53-mediated cell death and chemotherapy-induced apoptosis.

Conclusions:

  • p53 links programmed cell death to metabolic changes via extracellular adenosine sensing.
  • The p53-A2B axis represents a novel mechanism for cancer cell elimination.
  • This pathway connects cancer-associated metabolic alterations to therapeutic strategies.

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