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• W1909018478 abstract "// Jie Luo 1, 2, 3, 4, 5 , Soo Ok Lee 1, 2, 3, 4, 5 , Yun Cui 1, 2, 3, 4, 5 , Rachel Yang 1, 2, 3, 4, 5 , Lei Li 1, 2, 3, 4, 5, 6 , Chawnshang Chang 1, 2, 3, 4, 5, 7 1 Department of Pathology, University of Rochester, Rochester, NY 14642, USA 2 Department of Urology, University of Rochester, Rochester, NY 14642, USA 3 Department of Radiation Oncology, University of Rochester, Rochester, NY 14642, USA 4 Department of Biology, University of Rochester, Rochester, NY 14642, USA 5 The Wilmot Cancer Center, University of Rochester, Rochester, NY 14642, USA 6 Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital, Xian Jiaotong University, Xian 710061, China 7 Sex Hormone Research Center, China Medical University and Hospital, Taichung, 404, Taiwan Correspondence to: Chawnshang Chang, e-mail: chang@urmc.rochester.edu Lei Li, e-mail: lilydr@163.com Keywords: CCL5, bone marrow mesenchymal stem cells, HIF2α, androgen receptor, prostate cancer Received: February 26, 2015      Accepted: July 17, 2015      Published: July 27, 2015 ABSTRACT Several infiltrating cells in the tumor microenvironment could influence the cancer progression via secreting various cytokines. Here, we found the CCL5 secreted from BM-MSCs suppressed androgen receptor (AR) signals via enhancing the expression of hypoxia inducible factor 2α (HIF2α) in prostate cancer (PCa) cells. Mechanism dissection revealed that the increased HIF2α might alter the AR-HSP90 interaction to suppress the AR transactivation, and inhibition of HIF2α reversed the BM-MSCs-increased PCa stem cell population and PCa cells invasion. Importantly, CCL5 could suppress the prolyl hydroxylases (PHDs) expression, which might then lead to suppress VHL-mediated HIF2α ubiquitination. Together, these results demonstrated that the CCL5 signals from infiltrating BM-MSC cells to HIF2α signals within PCa cells might play a key role to increase PCa stem cell population and PCa metastasis via altering the AR signals. Targeting this newly identified CCL5/HIF2α/AR axis signal axis may allow us to develop a novel way to suppress PCa metastasis." @default.
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• W1909018478 date "2015-07-27" @default.
• W1909018478 modified "2023-09-22" @default.
• W1909018478 title "Infiltrating bone marrow mesenchymal stem cells (BM-MSCs) increase prostate cancer cell invasion<i>via</i>altering the CCL5/HIF2α/androgen receptor signals" @default.
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• W1909018478 doi "https://doi.org/10.18632/oncotarget.4515" @default.
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