This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sala, G. Articles by Falasca, M. Search for Related Content PubMed PubMed Citation Articles by Sala, G. Articles by Falasca, M.

Phospholipase C1 Is Required for Metastasis Development and Progression

¹ 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; ² Laboratory of Molecular Pharmacology, Department of Oncology, Istituto, di Ricerche Farmacologiche Mario Negri, Milan, Italy; and ³ Center of Excellence on Aging, G. d'Annunzio University Foundation, Chieti, Italy

Requests for reprints: Marco Falasca, 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, 4 Newark Street, London E1 2AT, United Kingdom. Phone: 44-0-20-7882-8243; Fax: 44-0-20-7882-2186; E-mail: m.falasca{at}qmul.ac.uk.

Key Words: cell invasion • cell migration • metastasis • phospholipase C • Rac

Cell motility and invasion play an essential role in the development of metastasis. Evidence suggests that the enzyme phospholipase C1 (PLC1) may be involved in tumor progression and possibly development of metastasis. In this study, we show that down-regulation of PLC1 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 PLC1 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 PLC1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. These data show a critical role of PLC1 in the metastatic potential of cancer cells, and they further indicate that PLC1 inhibition has a therapeutic potential in the treatment of metastasis dissemination. [Cancer Res 2008;68(24):10187–96]

This article has been cited by other articles:

				K. L. Everett, T. D. Bunney, Y. Yoon, F. Rodrigues-Lima, R. Harris, P. C. Driscoll, K. Abe, H. Fuchs, M. Hrabe de Angelis, P. Yu, et al. Characterization of Phospholipase C{gamma} Enzymes with Gain-of-Function Mutations J. Biol. Chem., August 21, 2009; 284(34): 23083 - 23093. [Abstract] [Full Text] [PDF]

				M. Beloueche-Babari, J. C. Peak, L. E. Jackson, M.-Y. Tiet, M. O. Leach, and S. A. Eccles Changes in choline metabolism as potential biomarkers of phospholipase C{gamma}1 inhibition in human prostate cancer cells Mol. Cancer Ther., May 1, 2009; 8(5): 1305 - 1311. [Abstract] [Full Text] [PDF]