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Study identifies 1 of the mechanisms behind breast cancer metastasis
Date:5/13/2010

BOSTON Several years ago, scientists at Beth Israel Deaconess Medical Center (BIDMC) and other laboratories made a paradoxical discovery regarding the Akt molecular pathway, a popular target for cancer drug therapies. They discovered that while one Akt protein Akt1 was actively preventing cancer cells from spreading, another closely related family member Akt2 was actually promoting breast cancer cell migration. And, indeed, subsequent studies in mouse models of breast cancer revealed that blocking the Akt pathway resulted in enhanced metastasis to the lungs.

This left scientists and clinicians faced with a troubling situation: Would the drugs actively being developed to inhibit Akt activity and halt breast cancer survival mechanisms be simultaneously enhancing cancer cells' abilities to metastasize to other organs?

Now, BIDMC scientists Alex Toker, PhD, and Rebecca Chin, PhD, have identified the first direct Akt1 target, a protein called palladin, providing an explanation for how Akt1 can function as a suppressor of breast cancer invasion and metastasis. This new finding, reported in the May 14, 2010 issue of the journal Molecular Cell, reveals another key piece of information as scientists continue their development of targeted cancer therapies, and underscores the importance of dissecting the precise mechanisms by which tumor cells invade and metastasize to distant organs.

"In 2005, after our lab had made the discovery that Akt was acting as something of a double agent, we wanted to delve into the mechanism that was accounting for opposing functions of these proteins during breast cancer progression," explains Toker, an Associate Professor of Pathology at BIDMC and Harvard Medical School (HMS). "We reasoned that identifying the specific molecular mechanisms by which Akt proteins either inhibit or promote cancer invasion and metastasis would be instrumental for developing more efficient targeted breast cancer therapies
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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