Phospholipase Cgamma1 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 Cgamma1 (PLCgamma1) may be involved in tumor progression and possibly development of metastasis. In this study, we show that down-regulation of PLCgamma1 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 PLCgamma1 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 PLCgamma1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. These data show a critical role of PLCgamma1 in the metastatic potential of cancer cells, and they further indicate that PLCgamma1 inhibition has a therapeutic potential in the treatment of metastasis dissemination.
Sala
Gianluca
G
Inositide Signalling Group, Centre for Diabetes and Metabolic Medicine, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom.
Dituri
Francesco
F
Raimondi
Claudio
C
Previdi
Sara
S
Maffucci
Tania
T
Mazzoletti
Marco
M
Rossi
Cosmo
C
Iezzi
Manuela
M
Lattanzio
Rossano
R
Piantelli
Mauro
M
Iacobelli
Stefano
S
Broggini
Massimo
M
Falasca
Marco
M
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000556:secondary*; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D051966:Phospholipase C gamma; D020830:rac1 GTP-Binding Protein