RESEARCHERS IDENTIFY KEY TO CANCER CELL MOBILITY

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RESEARCHERS IDENTIFY KEY TO CANCER CELL MOBILITY
06 November 2002 - University of Wisconsin-Madison

In the race to cure cancer, researchers look for roadblocks that could stop cancer in its tracks, preventing it from spreading to other parts of the body. Scientists from the University of Wisconsin-Madison may have found that blockade, an enzyme critical to the ability of cells to metastasize, a biological phenomenon by which cells migrate. The findings are published in the Nov. 7 issue of the journal Nature.

"The real, life-threatening problem with most cancers is that they migrate away from the initial site," says Richard Anderson, a UW-Madison pharmacology professor and senior author of the paper. "If we could regulate a cell's ability to move in a selective way, we may be able to block cancer metastasis."

Researchers have identified several important factors involved in cell migration, but they continue to search for the mechanisms that regulate these key factors. Anderson and his group have found that the enzyme, noted scientifically as PIPKIy661, appears to underpin cells' ability to move from organ to organ.

Cells can migrate through the body because they have small clusters of proteins called focal adhesions. When these clusters, located on the cell surface, respond to signals from molecules on other cells, they bind to those molecules. Once attached, the focal adhesions can pull the cell forward. Like wheels on a skateboard, these adhesions then give cells the ability to move around the body.

The key to blocking this movement, says Anderson, is inhibiting the assembly of focal adhesions. But, as he adds, these protein clusters result from the activity of several key factors, which receive their signals from a number of sources - proteins inside the cell or molecules outside it. To block focal adhesion assembly, one would have to block this other activity.

The key to doing that appears to be the enzyme, PIPKIy661, identified by Anderson and his colleagues, Kun Ling and Renee Doughman.

"What we've identified is an enzyme that regulates the assembly of focal adhesions," says Anderson. "Researchers have been looking for this enzyme for years."

PIPKIy661 interacts directly with two key proteins (FAK and talin) involved in focal adhesion assembly. At the same time, PIPKIy661 also generates an important second messenger (P14,5P2) that Anderson says both regulates a number of important proteins inside the cell and stimulates their ability to form focal adhesions.

Because of this enzyme's central role in regulating the factors involved in the assembly of focal adhesions, the researchers say it provides a promising target for developing drugs to prevent cancer cells from metastasizing.

"PIPKIy661 is like one of those circular (traffic) intersections in Italy and England," says Anderson. "There are all sorts of signals feeding in and out of it, and the traffic never stops." Changing the design of the intersection, he says, could change the flow of those signals.

By blocking the activity of PIPKIy661 - the intersection of focal adhesion assembly - cancer cells could become immobile, thereby unable to migrate to other parts of the body.

"Exactly how cancer cells metastasize has been poorly understood," says Anderson. "This discovery is a real breakthrough that could really have an impact."

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About: University of Wisconsin-Madison
In achievement and prestige, the University of Wisconsin-Madison has long been recognized as one of America’s great universities. A public, land-grant institution, UW-Madison offers a complete spectrum of liberal arts studies, professional programs and student activities. Many of its programs are hailed as world leaders in instruction, research and public service.

The university traces its roots to a clause in the Wisconsin Constitution, which decreed that the state should have a prominent public university. In 1848, Nelson Dewey, Wisconsin’s first governor, signed the act that formally created the university, and its first class, with 17 students, met in a Madison school building on February 5, 1849.

From those humble beginnings, the university has grown into a large, diverse community, with about 40,000 students enrolled each year. These students represent every state in the nation, as well as countries from around the globe, making for a truly international population.

UW-Madison is the oldest and largest campus in the University of Wisconsin System, a statewide network of 13 comprehensive universities, 13 freshman-sophomore transfer colleges and an extension service. One of two doctorate-granting universities in the system, UW-Madison’s specific mission is to provide "a learning environment in which faculty, staff and students can discover, examine critically, preserve and transmit the knowledge, wisdom and values that will help insure the survival of this and future generations and improve the quality of life for all."

The university achieves these ends through innovative programs of research, teaching and public service. Throughout its history, UW-Madison has sought to bring the power of learning into the daily lives of its students through innovations such as residential learning communities and service-learning opportunities. Students also participate freely in research, which has led to life-improving inventions from more fuel-efficient engines to cutting-edge genetic therapies.

Students, faculty and staff are motivated by a tradition known as the "Wisconsin Idea," described by UW President Charles Van Hise in 1904 as the compelling need to carry "the beneficent influence of the university ... to every home in the state." The Wisconsin Idea permeates the university’s work and helps forge close working relationships among university faculty and students and the state’s industries and government.

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