Potential New Target for Treatment of Neurofibromatosis Type 2

The proteins that provide cells with a sense of personal space could lead to a therapeutic target for neurofibromatosis type 2 (NF2), an inherited cancer disorder, according to researchers at The Wistar Institute and collaborating institutions. The findings, which appear in the April 12 issue of the journal Cancer Cell, could have profound implications for NF2 and related cancers, such as mesothelioma. The researchers describe, for the first time, that Merlin, the protein encoded by the NF2 gene interacts with a protein called angiomotin. This connection between Merlin and angiomotin also brings together two important information networks in cells, both of which have been implicated in numerous forms of cancer. It is a connection, the researchers say, between the sensors that detect interactions between cells and the signaling networks that drive cell division. "Angiomotin is required for movement of cells that form new blood vessels, so it is fascinating to see it so closely linked to Merlin, the product of the NF2 gene, loss of which leads to tumor formation," said Dr. Joseph Kissil, senior author of the study and associate professor in the Molecular and Cellular Oncogenesis Program of The Wistar Institute Cancer Center. "The discovery opens up a potential new method to treat NF2 by attacking the tumor cells directly and by starvation, a strategy already employed in certain cancer therapies. Drugs like Avastin, for example, target the growing blood vessels," Kissil said, "but what makes angiomotin a tempting target is that it is used by both blood vessels and the growing tumor cells that need the nutrients these blood vessels provide." NF2 is a genetic disorder caused by a mutation in both copies of a person's NF2 gene. It occurs in about one in every 30,000 people, and it is mostly hereditary.
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