Extracellular ATP enhances in vitro invasion of prostate cancer cells by activating Rho GTPase and upregulating MMPs expression

Zhang, Yang; Gong, Li-hua; Zhang, Hong-quan; Du, Qiang; You, Jiang-feng; Tian, Xin-xia; Fang, Wei-gang

doi:10.1016/j.canlet.2010.01.010

« Previous Next »Cancer Letters
Volume 293, Issue 2 , Pages 189-197, 28 July 2010

Extracellular ATP enhances in vitro invasion of prostate cancer cells by activating Rho GTPase and upregulating MMPs expression

Yang Zhang
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China
- These authors contributed equally to this work.
Li-hua Gong
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China
- These authors contributed equally to this work.
Hong-quan Zhang
- Departments of Histology and Embryology, Peking University Health Science Center, Beijing, China
Qiang Du
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China
Jiang-feng You
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China
Xin-xia Tian
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China
- Corresponding authors. Address: Department of Pathology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China. Tel.: +86 10 82802599; fax: +86 10 62015681.
Wei-gang Fang
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China
- Corresponding authors. Address: Department of Pathology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China. Tel.: +86 10 82802599; fax: +86 10 62015681.

Received 18 October 2009; received in revised form 4 January 2010; accepted 11 January 2010. published online 04 March 2010.

Abstract

We previously found that in addition to anti-proliferation function, extracellular ATP had a pro-invasion effect on prostate cancer cells, and probably serves as an important regulator of invasion in local microenvironment. However, the underlying mechanism remains unclear. In this study, we demonstrated that ATP increased the motility of prostate cancer cells, and promoted formation of lamellipodia and filopodia. We also found that ATP induced activation of Rac1 and Cdc42, and promoted expression of MMP-3 and MMP-13. These data suggest that extracellular ATP enhances the invasion of prostate cancer cells by activating Rho GTPases Rac1 and Cdc42 and upregulating MMPs expression.

Keywords: ATP, Prostate cancer, Invasion, Rho GTPase, MMP