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Hydrogen peroxide regulates cell adhesion through the redox sensor RPSA.

Filipe Vilas-Boas1, Ana Bagulho1, Rita Tenente1

  • 1Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.

Free Radical Biology & Medicine
|November 26, 2015
PubMed
Summary

Hydrogen peroxide (H2O2) drives tumor cell metastasis by oxidizing Ribosomal Protein SA (RPSA). Oxidized RPSA enhances cell adhesion and extravasation, revealing a new redox-based mechanism in cancer progression.

Keywords:
Cell adhesionExtravasationHydrogen peroxideIntegrin signalingRPSARedox signaling

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Metastasis requires tumor cells to gain new adhesion properties for migration and colonization.
  • Hydrogen peroxide (H2O2) is a key redox signaling molecule in the tumor microenvironment, influencing tumor development.
  • Molecular mechanisms of H2O2 action in tumor cells, particularly regarding adhesion, are not well understood.

Purpose of the Study:

  • Identify H2O2-target proteins in tumor cells.
  • Understand the role of these targets in tumor cell adhesion.
  • Explore novel redox-based therapeutic strategies for cancer.

Main Methods:

  • Identified Ribosomal Protein SA (RPSA) as a direct target of H2O2.
  • Observed accumulation of oxidized RPSA in clusters with adhesion molecules.
  • Assessed in vitro cell adhesion to laminin and in vivo cell extravasation.

Main Results:

  • RPSA oxidation was identified as a key H2O2-mediated event.
  • Oxidized RPSA clusters with specific adhesion molecules.
  • RPSA oxidation enhances tumor cell adhesion to laminin and promotes extravasation in vivo.

Conclusions:

  • RPSA acts as an H2O2 sensor, modulating cell adhesion properties.
  • This uncovers a novel H2O2-dependent mechanism regulating tumor cell metastasis.
  • High RPSA expression may provide a survival advantage to tumor cells in oxidative conditions.