P2X7 Mediates ATP-Driven Invasiveness in Prostate Cancer Cells |
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Authors: | Ying Qiu Wei-hua Li Hong-quan Zhang Yan Liu Xin-Xia Tian Wei-Gang Fang |
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Institution: | 1Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China;2Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China;3Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, 100191, China;University Paris Sud, France |
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Abstract: | The ATP-gated P2X7 has been shown to play an important role in invasiveness and metastasis of some tumors. However, the possible links and underlying mechanisms between P2X7 and prostate cancer have not been elucidated. Here, we demonstrated that P2X7 was highly expressed in some prostate cancer cells. Down-regulation of P2X7 by siRNA significantly attenuated ATP- or BzATP-driven migration and invasion of prostate cancer cells in vitro, and inhibited tumor invasiveness and metastases in nude mice. In addition, silencing of P2X7 remarkably attenuated ATP- or BzATP- driven expression changes of EMT/invasion-related genes Snail, E-cadherin, Claudin-1, IL-8 and MMP-3, and weakened the phosphorylation of PI3K/AKT and ERK1/2 in vitro. Similar effects were observed in nude mice. These data indicate that P2X7 stimulates cell invasion and metastasis in prostate cancer cells via some EMT/invasion-related genes, as well as PI3K/AKT and ERK1/2 signaling pathways. P2X7 could be a promising therapeutic target for prostate cancer. |
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