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AKT cancer cell pathway demonstrates unexpected function

BOSTON In investigating the molecular mechanisms of cancer cell motility the unique property that enables cancer to spread from its primary origin to other parts of the body researchers have uncovered a surprising role for the AKT/PKB (protein kinase B) enzyme, providing important new insights into cancer metastasis and suggesting that current efforts to develop cancer therapies by inhibiting AKT may be inadvertently promoting the spread of the disease.

Led by a scientific team at Beth Israel Deaconess Medical Center (BIDMC) and described in a study in the Nov. 23 issue of the medical journal Molecular Cell, the research demonstrates for the first time that AKT, which is known to increase cancer cells' survival capability also paradoxically blocks their motility and invasion abilities, thereby preventing cancer from spreading.

"The aggressive behavior of malignant cancer cells is determined by a complex array of signaling pathways that regulate key functions including cell proliferation, survival capacity, and the ability to migrate from their original location and invade other regions of the body," explains the study's senior author Alex Toker, Ph.D., a member of the department of pathology at BIDMC and associate professor of medicine at Harvard Medical School.

In the 1990s AKT, a component of the phosphoinositide 3-kinase (PI3K) signaling pathway, was first found to promote cancer cells' survival capacity, and since then the enzyme has also been shown to control cell proliferation.

"In essence, cancer cells have highjacked this enzyme and its regulatory proteins in order to increase their ability to survive," explains Toker. "By blocking the pathway and thereby causing cell death -- AKT has become a popular target in the development of cancer inhibitor drugs."

Although cell migration is an essential feature of the invasive phenotype of cancer cells, relatively little information has been available on AKT's role in th
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
22-Nov-2005


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