Metastasis is the ability of cancer cells to spread from a primary site, to form tumours at distant sites. It is a complex process in which cell motility and invasion play a fundamental role. Essential to our understanding of how metastasis develops is identification of the molecules, and characterisation of the mechanisms that regulate cell motility. Hitherto, these mechanisms have been poorly understood. Now, a team of researchers lead by Professor Marco Falasca at Barts and The London School of Medicine and Dentistry has shown not only that the enzyme phospholipase Cγ1 (PLCγ1) plays a crucial role in metastasis formation, but that down regulation of PLCγ1 expression is able to revert metastasis progression.
The team investigated the role of PLCγ1 in cell invasion and metastasis using different approaches to modulate its expression in highly invasive cancer cell lines. Their results showed that PLCγ1 is required for breast cancer cell invasion and activation of the protein Rac1. They revealed a functional link between PLCγ1 and Rac1 that provides insight into processes regulating cell invasion.
Professor Falasca explained: "Consistent with these data we detected an increase in PLC1 expression in metastases compared to primary tumours in breast cancer patients. Therefore PLCγ1 is critical for metastasis formation, and development and inhibition of this enzyme has a therapeutic potential in the treatment of metastasis dissemination."
"This is an exciting discovery. He has shown that turning off this molecule prevents metastasis. The simple fact is that if you stop metastasis, you stop cancer from killing people. We now need to focus on developing drugs that can block PLCγ1."
'Phospholipase Cγ1 is Required for Metastasis Development and Progression' is published in Cancer Research on Monday 15 December 2009.
The research was supported by The Association for International Cancer Research and by the European Commission FP6 program Apotherapy.
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Barts and The London School of Medicine and Dentistry
Barts and The London School of Medicine and Dentistry - at Queen Mary, University of London - offers international levels of excellence in research and teaching while serving a population of unrivalled diversity amongst which cases of diabetes, hypertension, heart disease, TB, oral disease and cancers are prevalent, within east London and the wider Thames Gateway. Through partnership with our linked trusts, notably Barts and The London NHS Trust, and our associated University Hospital trusts - Homerton, Newham, Whipps Cross and Queen's - the School's research and teaching is informed by an exceptionally wide ranging and stimulating clinical environment.
At the heart of the School's mission lies world class research, the result of a focused programme of recruitment of leading research groups from the UK and abroad and a £100 million investment in state-of-the-art facilities. Research is focused on translational research, cancer, cardiology, clinical pharmacology, inflammation, infectious diseases, stem cells, dermatology, gastroenterology, haematology, diabetes, neuroscience, surgery and dentistry.
The School is nationally and internationally recognised for research in these areas, reflected in the £40 million it attracts annually in research income. Its fundamental mission, with its partner NHS Trusts, and other partner organisations such as CRUK, is to ensure that that the best possible clinical service is underpinned by the very latest developments in scientific and clinical teaching, training and research.