Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity

• Juxiang Cao ^[5] ; Jennifer Schulte ^[5] ; Alexander Knight ^[1] ; Nicholas R Leslie ^[2] ; Agnieszka Zagozdzon ^[3] ; Roderick Bronson ^[3] ; Yefim Manevich ^[5] ; Craig Beeson ^[4] ; Carola A Neumann ^[5]
  1. [1] Whitworth University

     Whitworth University

     Estados Unidos

     
  2. [2] University of Dundee

     University of Dundee

     Reino Unido

     
  3. [3] Harvard Medical School

     Harvard Medical School

     City of Boston, Estados Unidos

     
  4. [4] Medical University of South Carolina

     Medical University of South Carolina

     Estados Unidos

     
  5. [5] Department of Cell and Molecular Pharmacology and Experimental Therapeutics Medical Medical University of South Carolina, Charleston, SC, USA

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 28, Nº. 10, 2009, págs. 1505-1517
• Idioma: inglés
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  • It is widely accepted that reactive oxygen species (ROS) promote tumorigenesis. However, the exact mechanisms are still unclear. As mice lacking the peroxidase peroxiredoxin1 (Prdx1) produce more cellular ROS and die prematurely of cancer, they offer an ideal model system to study ROS-induced tumorigenesis. Prdx1 ablation increased the susceptibility to Ras-induced breast cancer. We, therefore, investigated the role of Prdx1 in regulating oncogenic Ras effector pathways. We found Akt hyperactive in fibroblasts and mammary epithelial cells lacking Prdx1. Investigating the nature of such elevated Akt activation established a novel role for Prdx1 as a safeguard for the lipid phosphatase activity of PTEN, which is essential for its tumour suppressive function. We found binding of the peroxidase Prdx1 to PTEN essential for protecting PTEN from oxidation-induced inactivation. Along those lines, Prdx1 tumour suppression of Ras- or ErbB-2-induced transformation was mediated mainly via PTEN.