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Protein wields phosphate group to inhibit cancer metastasis
Date:1/3/2011

HOUSTON - By sticking a chemical group to it at a specific site, a protein arrests an enzyme that may worsen and spread cancer, an international research team led by scientists at The University of Texas MD Anderson Cancer Center reports in the January issue of Nature Cell Biology.

In addition to highlighting a novel anti-cancer pathway, the team found that the same deactivation of the enzyme called EZH2 is necessary for the formation of bone-forming cells from the stem cells that make them and other tissues.

"EZH2 is overexpressed in aggressive solid tumors and tied to cancer progression and metastasis," said the paper's senior author, Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology. "We have found that another protein, CDK1, deactivates EZH2."

The team's basic research findings provide a rationale for developing an EZH2 inhibitor or a drug that mimics the protein that deactivates it as new cancer drugs. "You have to understand the molecular details of cancer formation and progression to develop new therapies that improve treatment and prevention," Hung said.

In a series of experiments, the team demonstrated how CDK1 interferes with EZH2, reducing cell migration and invasion in breast cancer cell lines.

EZH2 silences gene expression by attaching a methyl group, which consists of one carbon and three hydrogen atoms, to a histone protein that is intertwined with DNA and other proteins to compose chromosomes. Genes suppressed by this methylation include tumor suppressors that would otherwise prevent cancer growth and spread.

The team showed that CDK1 short-circuits EZH2-mediated methylation by attaching a different chemical group consisting of one phosphate and three oxygen atoms to EZH2, a process called phosphorylation. And that phosphorylation has to occur at a specific amino acid on EZH2 to have this effect.

It's a matter of ph
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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