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Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
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AMPK/FOXO3a Pathway Increases Activity and/or Expression of ATM, DNA-PKcs, Src, EGFR, PDK1, and SOD2 and Induces

Yusuke Urushihara1,2, Takuma Hashimoto1, Yohei Fujishima1,3

  • 1Department of Radiation Biology, School of Medicine, Tohoku University, Sendai 980-8575, Japan.

International Journal of Molecular Sciences
|August 26, 2023
PubMed

Insights

Nutrient starvation enhances cancer cell survival against radiation by activating AMPK and FOXO3a. Targeting these molecules may improve cancer radiosensitization therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Solid tumors often feature hypoxic and nutrient-deprived areas.
  • Cancer cells in these conditions can develop resistance to radiation therapy.
  • Previous work linked nutrient starvation to increased DNA repair proteins ATM and DNA-PKcs.

Purpose of the Study:

  • To investigate the molecular mechanisms of nutrient starvation-induced radioresistance.
  • To elucidate the roles of AMPK and FOXO3a in this cellular response.

Main Methods:

  • Utilized MDA-MB-231 cells under nutrient starvation conditions.
  • Examined the expression and activity of key proteins including AMPKα, FOXO3a, ATM, DNA-PKcs, Src, EGFR, PDK1, and SOD2.
  • Employed siRNA to knock down AMPKα and FOXO3a to assess their impact.

Main Results:

  • Nutrient starvation increased cell survival post-irradiation and upregulated proteins like AMPKα, FOXO3a, ATM, DNA-PKcs, Src, EGFR, PDK1, and SOD2.
  • Knockdown of AMPKα or FOXO3a reversed these increases under starvation.
  • Nutrient starvation reduced apoptosis after irradiation, an effect reversed by FOXO3a knockdown.

Conclusions:

  • AMPK and FOXO3a are crucial in mediating radioresistance under nutrient deprivation.
  • These proteins represent potential therapeutic targets for enhancing radiosensitization in cancer treatment.
Keywords:
AMPKATMDNA-PKcsEGFRFOXO3aPDK1SOD2apoptosisnutrient starvationradiation sensitivity

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