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]
Phospholipase Cgamma1 is required for metastasis development and progression / Sala, Gianluca; Dituri, F; Raimondi, C; Previdi, S; Maffucci, T; Mazzoletti, M; Rossi, Carmen; Iezzi, Manuela; Lattanzio, Rossano; Piantelli, Mauro; Iacobelli, Stefano; Broggini, M; Falasca, Marco. - In: CANCER RESEARCH. - ISSN 0008-5472. - 68(24):(2008), pp. 10187-10196. [10.1158/0008-5472.CAN-08-1181]
Phospholipase Cgamma1 is required for metastasis development and progression
FALASCA, Marco
2008-01-01
Abstract
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]I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
