Tuesday, 23 April 2013 20:00

Pulling the Plug on Glioblastoma Signaling

Written by  Claire Walczak
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With the death from brain cancer of Senator Ted Kennedy in 2009, gliobastoma multiforme (GBM), made a brief but frightening appearance in the news. GBM is a bitter diagnosis with a poor prognosis. More than half the patients will die within one year and the five-year survival rate is approximately 5%. Why is this cancer so deadly? Traditionally, solid tumor within the brain can be removed surgically or treated with radiation. However, cells within gliomas are like jellyfish with tiny tentacles infiltrating different parts of the brain. This makes it all but impossible to surgically remove the entire tumor while radiation is often ineffective in killing off all of the tumor cells.

Clearly researchers need to find better ways of treating glioblastomas. In the January 15th issue of Molecular Biology of the Cell, Steve Rosenfeld and colleagues propose a new strategy.

One critical aspect of glioblastomas is that these cells can migrate rapidly, spreading tumors throughout the brain. Previous attempts to target the signals that tell the cells to spread had little therapeutic success. The reason, say Rosenfeld and colleagues, is that these tumors are responding to multiple signals (cell signaling) with the same repeated message, grow and move. Inhibit one signal and a different signal will deliver the same message. Instead, their researchers sought a common node or intersection point of the signals to block all messages to the tumors.

It turns out that these cells use machinery of the cytoskeleton to migrate. One important player is a motor protein called myosin, which coordinates with the actin cytoskeleton during cell migration. Myosin is a major component of muscle, but there are many types of myosins with specialized functions in certain cells. The brain contains low levels of a special myosin, called myosin II, but certain gliomas have high levels of myosin II that can be targeted by drugs. Rosenfeld and colleagues show that inhibitors of myosin II effectively blocked invasion in laboratory models of glioma, opening a new line of attack on this deadly cancer.

CellTweet #6. Citation: Mol Biol Cell. 2012 Feb; 23(4):533-42. Epub 2012 Jan 4

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