Phospholipase Cγ1 Is Required for Metastasis Development and Progression

被引：101

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

来源：

CANCER RESEARCH | 2008年 / 68卷 / 24期

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

页码：10187 / 10196

页数：10

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