TY - JOUR
T1 - Phospholipase Cγ1 is required for metastasis development and progression
AU - Sala, Gianluca
AU - Dituri, Francesco
AU - Raimondi, Claudio
AU - Previdi, Sara
AU - Maffucci, Tania
AU - Mazzoletti, Marco
AU - Rossi, Cosmo
AU - Iezzi, Manuela
AU - Lattanzio, Rossano
AU - Piantelli, Mauro
AU - Iacobelli, Stefano
AU - Broggini, Massimo
AU - Falasca, Marco
PY - 2008/12/15
Y1 - 2008/12/15
N2 - Cell motility and invasion play an essential role in the development of metastasis. Evidence suggests that the enzyme phospholipase Cγ1 (PLCγ1) may be involved in tumor progression and possibly development of metastasis. In this study, we show that down-regulation of PLCγ1 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 PLCγ1 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 PLCγ1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. These data showa critical role of PLCγ1 in the metastatic potential of cancer cells, and they further indicate that PLCγ1 inhibition has a therapeutic potential in the treatment of metastasis dissemination.
AB - Cell motility and invasion play an essential role in the development of metastasis. Evidence suggests that the enzyme phospholipase Cγ1 (PLCγ1) may be involved in tumor progression and possibly development of metastasis. In this study, we show that down-regulation of PLCγ1 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 PLCγ1 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 PLCγ1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. These data showa critical role of PLCγ1 in the metastatic potential of cancer cells, and they further indicate that PLCγ1 inhibition has a therapeutic potential in the treatment of metastasis dissemination.
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U2 - 10.1158/0008-5472.CAN-08-1181
DO - 10.1158/0008-5472.CAN-08-1181
M3 - Article
C2 - 19074886
AN - SCOPUS:57749118818
VL - 68
SP - 10187
EP - 10196
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 24
ER -