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Blocking the critical structure that lets cancer cells move -- their feet
Date:12/16/2010

DURHAM, N.C. -- Scientists now know that some cancer cells spread, or metastasize, throughout the body the old-fashioned way -- by using their feet. But researchers at Duke Cancer Institute have discovered a way to short-circuit their travels by preventing the development of these feet, called invadopodia. This discovery is even more important because preventing the development of these "feet" also eliminates the action of proteins present in the feet that burn through intact tissue and let cancer cells enter new cells.

The results could yield a treatment to prevent the spread of cancer, which would be taken in combination with a treatment that kills the cancer cells, said Ann Marie Pendergast, Ph.D., senior author and James B. Duke Professor of Pharmacology and Cancer Biology at Duke. "A combination like this would be more effective than either treatment given alone."

"This is the first time anyone has identified the Abl family of protein kinases (comprising two proteins, Abl and Arg) as critical regulators of invadopodia structures," Pendergast said. "This has never been seen before."

The study was published in the Journal of Biological Chemistry on Dec. 17.

The team found that the Abl and Arg kinases are required not only for the formation and function of the invadopodia, but also that these kinases are found within these structures. "Thus, if we can find a way to block the kinases, we'll find a way to keep the feet from forming correctly and will keep the cells from moving," Pendergast said.

The researchers also made a new connection between these Abl and Arg kinases and the regulation of a Matrix Metalloproteinase (MMP) that is very important in cancer invasion and metastasis. "When you lose the functions of the Abl and Arg kinases, you also lose the function of the MMP proteins, which 'chew' through the matrix surrounding cells and tissues," Pendergast said. The MMP proteins can create openings for can
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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