title: Phospholipase Cgamma1 is required for metastasis development and progression.
abstract: 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.
authors.affiliation: 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.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sala
authors.forename: Francesco
authors.initials: F
authors.lastname: Dituri
authors.forename: Claudio
authors.initials: C
authors.lastname: Raimondi
authors.forename: Sara
authors.initials: S
authors.lastname: Previdi
authors.forename: Tania
authors.initials: T
authors.lastname: Maffucci
authors.forename: Marco
authors.initials: M
authors.lastname: Mazzoletti
authors.forename: Cosmo
authors.initials: C
authors.lastname: Rossi
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Rossano
authors.initials: R
authors.lastname: Lattanzio
authors.forename: Mauro
authors.initials: M
authors.lastname: Piantelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Iacobelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Broggini
authors.forename: Marco
authors.initials: M
authors.lastname: Falasca
mesh_terms: 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
chemical_list: D051966:Phospholipase C gamma; D020830:rac1 GTP-Binding Protein