Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, PR China.
Cancer Lett. 2010 Jul 28;293(2):189-97. doi: 10.1016/j.canlet.2010.01.010. Epub 2010 Mar 3.
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.
我们之前发现,细胞外 ATP 除了具有抗增殖功能外,对前列腺癌细胞还有促侵袭作用,可能作为局部微环境中侵袭的重要调节剂。然而,其潜在机制尚不清楚。在这项研究中,我们证明了 ATP 增加了前列腺癌细胞的迁移能力,并促进了片状伪足和丝状伪足的形成。我们还发现,ATP 诱导 Rac1 和 Cdc42 的激活,并促进 MMP-3 和 MMP-13 的表达。这些数据表明,细胞外 ATP 通过激活 Rho GTPases Rac1 和 Cdc42 以及上调 MMPs 的表达来增强前列腺癌细胞的侵袭能力。