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

Cancer Lett. 2010 Jul 28;293(2):189-97. doi: 10.1016/j.canlet.2010.01.010. Epub 2010 Mar 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Cell Line, Tumor
  • Cell Movement
  • Extracellular Space
  • Humans
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Invasiveness / pathology*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • Signal Transduction / drug effects
  • Up-Regulation
  • cdc42 GTP-Binding Protein / metabolism*
  • rac1 GTP-Binding Protein / metabolism*
  • rho GTP-Binding Proteins / metabolism

Substances

  • RAC1 protein, human
  • Adenosine Triphosphate
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinases
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins