Phospholipase Cγ1 Is Required for Metastasis Development and Progression

Cell motility and invasion play an essential role in the development of metastasis. Evidence suggests that the enzyme phospholipase C gamma 1 (PLC gamma 1) may be involved in tumor progression and possibly development of metastasis. In this study, we show that down-regulation of PLC gamma 1 expression severely impairs activation of the small GTP-binding protein Rac and cell invasion in breast cancer cell lines and U87 in vitro. Experimental metastasis assays in nude mice show that inducible knockdown of PLC gamma 1 strongly inhibits development of MDA-MB-231-derived lung metastasis and reverts metastasis formation. In addition, analysis of 60 breast cancer patients' tissues revealed an increase of PLC gamma 1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. These data show a critical role of PLC gamma 1 in the metastatic potential of cancer cells, and they further indicate that PLC gamma 1 inhibition has a therapeutic potential in the treatment of metastasis dissemination. [Cancer Res 2008;68(24):10187-96]