ROS enhances CXCR4-mediated functions through inactivation of PTEN in prostate cancer cells

► ROS increased phospho-AKT and CXCR4 expression in prostate cancer cells. ► ROS mediated PTEN inactivation, but did not affect expression. ► ROS enhanced cell migration and invasion, in a CXCR4 dependent manner. Inactivation of the tumor suppressor phosphatase and tensin homolog deleted on chromoso...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2011-07, Vol.410 (2), p.195-200
Main Authors: Chetram, Mahandranauth A., Don-Salu-Hewage, Ayesha S., Hinton, Cimona V.
Format: Article
Language:English
Subjects:
AKT
Cell Line, Tumor
CXCR4
H2O2
Humans
Hydrogen Peroxide - pharmacology
Male
Prostate cancer
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
PTEN
PTEN Phosphohydrolase - metabolism
Reactive Oxygen Species - metabolism
Reactive Oxygen Species - pharmacology
Receptors, CXCR4 - metabolism
ROS
Tumor Microenvironment
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Summary:► ROS increased phospho-AKT and CXCR4 expression in prostate cancer cells. ► ROS mediated PTEN inactivation, but did not affect expression. ► ROS enhanced cell migration and invasion, in a CXCR4 dependent manner. Inactivation of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is heavily implicated in the tumorigenesis of prostate cancer. Conversely, the upregulation of the chemokine (CXC) receptor 4 (CXCR4) is associated with prostate cancer progression and metastasis. Studies have shown that loss of PTEN permits CXCR4-mediated functions in prostate cancer cells. Loss of PTEN function is typically due to genetic and epigenetic modulations, as well as active site oxidation by reactive oxygen species (ROS); likewise ROS upregulates CXCR4 expression. Herein, we show that ROS accumulation permitted CXCR4-mediated functions through PTEN catalytic inactivation. ROS increased p-AKT and CXCR4 expression, which were abrogated by a ROS scavenger in prostate cancer cells. ROS mediated PTEN inactivation but did not affect expression, yet enhanced cell migration and invasion in a CXCR4-dependent manner. Collectively, our studies add to the body of knowledge on the regulatory role of PTEN in CXCR4-mediated cancer progression, and hopefully, will contribute to the development of therapies that target the tumor microenvironment, which have great potential for the better management of a metastatic disease.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2011.05.074