title: ROS enhances CXCR4-mediated functions through inactivation of PTEN in prostate cancer cells.
abstract: 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.
authors.affiliation: Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA 30314, USA.
authors.forename: Mahandranauth A
authors.initials: MA
authors.lastname: Chetram
authors.forename: Ayesha S
authors.initials: AS
authors.lastname: Don-Salu-Hewage
authors.forename: Cimona V
authors.initials: CV
authors.lastname: Hinton
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: C527276:CXCR4 protein, human; D017382:Reactive Oxygen Species; D019718:Receptors, CXCR4; D006861:Hydrogen Peroxide; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human