Phospholipase Cγ1 Is Required for Metastasis Development and Progression

被引:100
|
作者
Sala, Gianluca [1 ]
Dituri, Francesco [1 ]
Raimondi, Claudio [1 ]
Previdi, Sara [2 ]
Maffucci, Tania [1 ]
Mazzoletti, Marco [2 ]
Rossi, Cosmo [3 ]
Iezzi, Manuela [3 ]
Lattanzio, Rossano [3 ]
Piantelli, Mauro [3 ]
Iacobelli, Stefano [3 ]
Broggini, Massimo [2 ]
Falasca, Marco [1 ]
机构
[1] Univ London, Barts & London Sch Med & Dent, Inst Cell & Mol Sci, Ctr Diabet & Metab Med,Inositide Signalling Grp, London E1 2AT, England
[2] Ist Ric Farmacol Mario Negri, Dept Oncol, Mol Pharmacol Lab, Milan, Italy
[3] Univ G dAnnunzio, Ctr Excellence Aging, Chieti, Italy
关键词
D O I
10.1158/0008-5472.CAN-08-1181
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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]
引用
收藏
页码:10187 / 10196
页数:10
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