P2X7 mediates ATP-driven invasiveness in prostate cancer cells

Ying Qiu; Wei-Hua Li; Hong-Quan Zhang; Yan Liu; Xin-Xia Tian; Wei-Gang Fang

doi:10.1371/journal.pone.0114371

P2X7 mediates ATP-driven invasiveness in prostate cancer cells

PLoS One. 2014 Dec 8;9(12):e114371. doi: 10.1371/journal.pone.0114371. eCollection 2014.

Authors

Ying Qiu¹, Wei-Hua Li¹, Hong-Quan Zhang², Yan Liu¹, Xin-Xia Tian¹, Wei-Gang Fang¹

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China; Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
² Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China; Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, 100191, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism*
Animals
Cell Line, Tumor
Cell Movement / genetics
Disease Models, Animal
Epithelial-Mesenchymal Transition / genetics
Gene Expression
Gene Knockdown Techniques
Humans
MAP Kinase Signaling System
Male
Mice
Neoplasm Metastasis
Phosphatidylinositol 3-Kinases / metabolism
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / pathology
Proto-Oncogene Proteins c-akt / metabolism
Receptors, Purinergic P2X7 / genetics*
Receptors, Purinergic P2X7 / metabolism

Substances

Receptors, Purinergic P2X7
Adenosine Triphosphate
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by grants to WGF from National Natural Science Foundation of China (81321003, 30971152), and 973 Program (2010CB529402) from the Ministry of Science and Technology of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.