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Researchers find coupling of proteins promotes glioblastoma development
Date:10/21/2011

Two previously unassociated proteins known to be overly active in a variety of cancers bind together to ignite and sustain malignant brain tumors, a research team led by scientists at The University of Texas MD Anderson Cancer Center reports this week in the journal Cancer Cell.

This research is the first to connect FoxM1 to a molecular signaling cascade that regulates normal neural stem cells, said senior author, Suyun Huang, M.D., Ph.D., associate professor in MD Anderson's Department of Neurosurgery.

"When FoxM1 binds to beta-catenin, we found that it also supports the self-renewal and differentiation of glioma- initiating cells, cancer stem cells thought to drive glioblastoma multiforme," Huang said.

Glioblastoma multiforme is the most common and lethal form of brain tumor. Glioma- initiating cells are prime suspects in the disease's resistance to treatment and ability to reoccur.

Protein's connection could be drug target

The scientists established the relationship between FoxM1 and beta-catenin in a series of cell line experiments and then confirmed their findings in mouse models of human glioblastoma and in an analysis of human tumors.

FoxM1 and beta-catenin separately so far have largely evaded targeting by drugs. Huang and her team are focusing on the details of the connection between the two proteins in search of small molecules that might block their binding.

"Our study might lead to the development of a new class of small-molecule anti-cancer drugs, including but not necessarily limited to glioblastoma multiforme," Huang said. Much preclinical work remains before such a drug can be identified and brought to clinical trial.

Blocking FoxM1 reduces glioblastoma in mice 100 percent

FoxM1 previously was known solely as a transcription factor a protein that binds to the DNA in a gene's promoter region to prompt the gene's expression of messenger RNA
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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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