PTRF-cavin-1 expression decreases the migration of PC3 prostate cancer cells: role of matrix metalloprotease 9

Abstract

Caveolae are specialized plasma membrane subdomains with a distinct lipid and protein composition, which play an essential role in cell physiology by performing trafficking and signalling functions. The structure and functions of caveolae have been shown to require caveolin-1, a major protein component of caveolae. Caveolin-1 expression and secretion are increased in metastatic prostate cancer, and caveolin-1 seems to contribute to prostate cancer growth and metastasis. Recently, a cytoplasmic protein named PTRF (Polymerase I and Transcript Release Factor) or cavin-1 was found to be required, in concert with caveolin-1, for the formation and functions of caveolae. Genetic ablation of PTRF results in loss of caveolae while caveolin-1 is still expressed, albeit at reduced level, but associates with flat plasma membrane. In metastatic PC3 prostate cancer cells that express abundant caveolin-1 but no PTRF, heterologous PTRF expression restores caveola formation and caveolin-1 distribution (Hill et al., 2008; Cell 132, 113-124). We now show that PTRF/cavin-1-expressing PC3 cells exhibit decreased migration, and that this effect is mediated by reduced MMP9 production. PTRF/cavin-1, and to a lesser extent, cavin-2, -3, and -4 all decreased MMP9. We further show that the PTRF/cavin-1-mediated reduction of MMP9 production is independent of caveola formation. Taken together, our results suggest that PTRF/cavin-1 expression alters prostate cancer aggressiveness.