P2X7 Mediates ATP-Driven Invasiveness in Prostate Cancer Cells

被引:104
|
作者
Qiu, Ying [1 ,2 ]
Li, Wei-hua [1 ,2 ]
Zhang, Hong-quan [1 ,3 ]
Liu, Yan [1 ,2 ]
Tian, Xin-Xia [1 ,2 ]
Fang, Wei-Gang [1 ,2 ]
机构
[1] Peking Univ, Hlth Sci Ctr, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100191, Peoples R China
[2] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pathol, Beijing 100191, Peoples R China
[3] Peking Univ, Hlth Sci Ctr, Dept Anat Histol & Embryol, Beijing 100191, Peoples R China
来源
PLOS ONE | 2014年 / 9卷 / 12期
基金
中国国家自然科学基金;
关键词
P2X(7) RECEPTOR EXPRESSION; EXTRACELLULAR ATP; IN-VITRO; PURINERGIC RECEPTORS; METASTASIS; PROLIFERATION; INTERLEUKIN-8; CALCIUM; GROWTH; VIVO;
D O I
10.1371/journal.pone.0114371
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:22
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