Metastasis Process Halted with Enzyme Blocker

In a remarkable development, a team of researchers has revealed not only that the enzyme phospholipase Cγ1 (PLCγ1) plays a critical role in metastasis formation, but that downregulation of PLCγ1 expression is able to revert metastasis progression.

Metastasis is the ability of cancer cells to spread from a primary site, to form tumors at distant sites. It is a complicated mechanism in which cell motility and invasion play an essential role. Fundamental to the understanding of how metastasis develops is identification of the molecules, and characterization of the mechanisms that regulate cell motility. Up until now, these processes have been poorly understood.

The scientists, led by researchers Prof. Marco Falasca, from Barts and The London School of Medicine and Dentistry (UK), investigated the role of PLCγ1 in cell invasion and metastasis using different approaches to modulate its expression in highly invasive cancer cell lines. The study's findings demonstrated that PLCγ1 is required for breast cancer-cell invasion and activation of the protein Rac1. The investigators discovered a functional link between PLCγ1 and Rac1 that provides insight into processes regulating cell invasion.

Prof. Falasca explained, "Consistent with these data we detected an increase in PLC1 expression in metastases compared to primary tumors 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. [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 PLCγ1.”

The study was published in the December 15, 2008, issue of the journal Cancer Research.

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Barts and The London School of Medicine and Dentistry