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Updated: Jan 26, 2026

Dissipative Microgravimetry to Study the Binding Dynamics of the Phospholipid Binding Protein Annexin A2 to Solid-supported Lipid Bilayers Using a Quartz Resonator
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Annexin A2 Regulates AKT Upon H₂O₂-Dependent Signaling Activation in Cancer Cells

Stéphanie Anais Castaldo1, Tom Ajime2, Gisela Serrão3

  • 1Centre for Biomedical Research (CBMR), Campus of Gambelas, University of Algarve, Building 8, Room 2.22, 8005-139 Faro, Portugal. stephanie.castaldo@cme.vib-kuleuven.be.

Cancers
|April 10, 2019
PubMed

Insights

Annexin A2 (ANXA2) regulates hydrogen peroxide (H₂O₂) signaling in cancer by interacting with PTEN, a key inhibitor of the AKT pathway. This interaction impacts tumor progression and peroxiredoxin 2 expression.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Hydrogen peroxide (H₂O₂) acts as a crucial second messenger in oncogenic signaling pathways, including Ras and growth factor receptor pathways.
  • Oxidation of redox-sensitive cysteine residues in proteins by H₂O₂ alters protein structure and function, impacting cellular processes.
  • Annexin A2 (ANXA2) has been identified as a redox-regulatory protein involved in oxidative stress response and tumor promotion.

Purpose of the Study:

  • To investigate the role of ANXA2 in regulating H₂O₂-dependent signaling pathways that drive tumor progression.
  • To elucidate the mechanism by which ANXA2 influences the PI3K/AKT signaling cascade.
  • To explore the relationship between ANXA2, PTEN, and peroxiredoxin 2.

Main Methods:

  • Depletion of ANXA2 using genetic techniques.
  • Stimulation with epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) and oncogenic Ras.
  • Analysis of AKT phosphorylation at Ser 473.
  • Co-expression studies with PTEN and ANXA2 (wild-type and Cys-8-Ala mutant).
  • Assessment of peroxiredoxin 2 expression in a reactive oxygen species-dependent manner.

Main Results:

  • ANXA2 depletion enhanced AKT activation following EGF/EGFR stimulation or oncogenic Ras transformation.
  • ANXA2, through its reactive Cys-8 residue, binds to PTEN.
  • Co-expression of PTEN and wild-type ANXA2, but not the Cys-8-Ala mutant, inhibited AKT phosphorylation on Ser 473.
  • ANXA2 was found to inversely regulate peroxiredoxin 2 expression in a reactive oxygen species-dependent manner.

Conclusions:

  • ANXA2 plays a significant role in regulating PTEN within the PI3K/AKT signaling cascade.
  • ANXA2 modulates H₂O₂-dependent signaling, impacting tumor progression.
  • ANXA2 influences peroxiredoxin 2 expression, suggesting a broader role in redox homeostasis during tumorigenesis.
Keywords:
ANXA2H2O2-dependent signalingPI3K/AKTPRDX2PTEN

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