Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity

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 tumori...

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Bibliographic Details
Published in:The EMBO journal 2009-05, Vol.28 (10), p.1505-1517
Main Authors: Cao, Juxiang, Schulte, Jennifer, Knight, Alexander, Leslie, Nicholas R, Zagozdzon, Agnieszka, Bronson, Roderick, Manevich, Yefim, Beeson, Craig, Neumann, Carola A
Format: Article
Language:English
Subjects:
Animals
Breast cancer
Cellular biology
EMBO24
Epithelial Cells - enzymology
Fibroblasts - enzymology
Inactivation
Inhibitor drugs
Mice
Mice, Knockout
Molecular biology
Neoplasms - chemically induced
Neoplasms - prevention & control
Oxidation
oxidative stress
peroxiredoxin1
Peroxiredoxins - deficiency
Peroxiredoxins - physiology
Proto-Oncogene Proteins c-akt - metabolism
PTEN phosphatase
PTEN Phosphohydrolase - metabolism
Reactive Oxygen Species - metabolism
Reactive Oxygen Species - toxicity
Rodents
transformation
Tumors
tumour initiation
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2009.101