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 in the cover story of the October 18, 2011 issue of Cancer Cell. This research is the first to connect FoxM1 to a molecular signaling cascade that regulates normal neural stem cells, said senior author, Dr. Suyun Huang, 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," Dr. 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. 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 have so far largely evaded targeting by drugs. Dr. 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," Dr. Huang said. Much preclinical work remains to be done before such a drug can be identified and brought to clinical trial. FoxM1 was previously 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 that is processed into a protein.
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