Breast Cancer Metastasis Requires Phospholipase Activity

They reported in the December 15, 2008, issue of the journal Cancer Research that down-regulation of PLC-gamma-1 expression severely impaired activation of the small GTP-binding protein Rac and cell invasion in breast cancer cell lines growing in laboratory cultures. The Rac1 protein is a GTPase belonging to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.

Experimental metastasis assays in nude mice showed that inducible knockdown of PLC-gamma-1 strongly inhibited development of MDA-MB-231–derived lung metastasis and reverted metastasis formation. Furthermore, analysis of tissues obtained from 60 breast cancer patients revealed an increase of PLC-gamma-1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. Senior author Dr. Marco Falasca, professor of metabolic medicine at Queen Mary, University of London, explained, "Consistent with these data we detected an increase in PLC-gamma-1 expression in metastases compared to primary tumors in breast cancer patients. Therefore, PLC-gamma-1 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. We have 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 PLC-gamma-1."

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Queen Mary, University of London