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  11. Tumor Suppressor P53 Stole The Akt In Hypoxia.

Tumor suppressor p53 stole the AKT in hypoxia.

Zhong Yun, Peter M Glazer

    The Journal of Clinical Investigation
    |May 12, 2015

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    View abstract on PubMed

    Summary
    This summary is machine-generated.

    Hypoxia in tumors worsens outcomes, especially with p53 loss. Researchers found a six-gene signature linked to apoptosis and poor outcomes, suggesting AKT inhibition as a cancer therapy.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cancer Research

    Background:

    • Tumor hypoxia is linked to poor prognosis and is often worsened by p53 tumor suppressor loss.
    • While functional p53 promotes apoptosis under hypoxia, the specific p53-dependent genes involved remain unclear.

    Purpose of the Study:

    • To identify p53-dependent genes induced by hypoxia that mediate apoptosis.
    • To investigate the role of AKT signaling in p53-mediated apoptosis under hypoxic conditions.
    • To evaluate the therapeutic potential of AKT inhibition in combination with radiation for hypoxic cancers.

    Main Methods:

    • Identification of a six-gene signature specifically induced by hypoxia in a p53-dependent manner.
    • Analysis of gene signature downregulation in various cancer patient cohorts.

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    Induction and Testing of Hypoxia in Cell Culture
    07:01

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    Published on: August 12, 2011

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  • Assessment of AKT inhibition's role in p53-mediated apoptosis.
  • Evaluation of combined AKT inhibitor and ionizing radiation treatment in p53-deficient xenograft models.

    • Main Results:

    • A six-gene signature mediating p53-dependent apoptosis under hypoxia was identified.
    • Downregulation of this signature correlated with poor clinical outcomes across diverse cancers.
    • AKT inhibition was found to mediate p53-dependent apoptosis induction under hypoxia.
    • Combined AKT inhibition and ionizing radiation significantly reduced tumor size in a p53-deficient model.

    Conclusions:

    • The study elucidates key p53-dependent genes and pathways involved in hypoxic apoptosis.
    • AKT inhibition shows therapeutic promise for inducing apoptosis in hypoxic, p53-deficient cancers.
    • Targeting AKT signaling could be a viable strategy for improving cancer treatment outcomes.