Navigation Links
Study identifies 1 of the mechanisms behind breast cancer metastasis

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."

As with many proteins in cancerous cells, Akt actually exists as a "family" of related proteins, consisting of Akt1, Akt2 and Akt3, explains Chin, an Instructor of Pathology at BIDMC and HMS. "In breast cancer, Akt1 and Ak2 are found, and are frequently hyperactivated due to genetic mutations in the pathway. But we now know that the two family members have opposing functions such that Akt1 inhibits, while Akt2 enhances invasion into the local tumor stroma, leading to metastasis."

To identify novel downstream targets of Akt proteins in breast cancer, the scientists used a discovery-based proteomics approach, coupled with analyses of breast cancer cell lines derived from patients with aggressive metastatic disease. This widely used approach led the authors to identify palladin, a protein known to regulate cell motility and named after the Italian Renaissance architect Andrea Palladio and the Palladian style of architecture.

"Palladin's normal function is to inhibit cell migration and keep cells in place," explains Toker. "By organizing the cellular cytoskeleton at the molecular level, palladin maintains the architecture of the cell in a highly organized manner." But, he adds, because Akt1 regulates palladin in an exclusive manner (by blocking cell motility) when palladin is lost, cells become disorganized, leading to a marked increase in cell migration. "It is believed that the end result is enhanced metastasis, a hypothesis that our lab is continuing to investigate using mouse models of disease progression," notes Toker.

Since the mid-1990s, scientists have known that there exist more than 100 targets of Akt proteins. "But among all of these, only a handful have been shown to be specific to either Akt1 or Akt2," adds Toker. "Our discovery really is the first example of this type of specific mechanism in the Akt pathway, and understanding specific targets is of enormous importance for pharmacological purposes."


Contact: Bonnie Prescott
Beth Israel Deaconess Medical Center

Related medicine news :

1. Study shows costs and benefits of testosterone in birds
2. Study finds rotavirus vaccine greatly reduces hospitalizations for acute gastroenteritis in children
3. Childhood psychological problems create long-term economic losses, study finds
4. HIRC Research Alert: New Study Identifies Best Pharmaceutical Company Account Managers and Program Offerings
5. Study demonstrates art therapys effectiveness in pediatric asthma
6. Brain Cell Study Explains Eureka Moment
7. Study Challenges Key Autism Theory
8. New study suggests sickle cell disease may affect brain function in adults
9. Once-A-Year Vitamin D Megadose Ups Fracture Risk: Study
10. Genetic Variants Tied to MS, Study Finds
11. UT Southwestern participates in nationwide study offering free lung tumor genetic testing
Post Your Comments:
(Date:11/30/2015)... , ... November 30, 2015 , ... ... Beard and Brooke Bennett are collaborating with brands across various categories through traditional ... influential figures make up an elite group of Gold Medal Moms who can ...
(Date:11/30/2015)... Garden City, NY (PRWEB) , ... December 01, 2015 , ... ... as a 2015-2016 inductee into its VIP Woman of the Year Circle. She ... is the nation’s leading networking organization exclusively for professional women, boasting more than 850,000 ...
(Date:11/30/2015)... ... 2015 , ... Being a caregiver for someone you love ... Care System, the Caregiver Support Program promotes the health and wellbeing of family ... percent report that their role as a caregiver has created marital strain,” said ...
(Date:11/30/2015)... ... November 30, 2015 , ... According to research by ... require dental technicians to be certified or obtain continuing education. To increase awareness ... In Your Mouth?” campaign to inform dentists that the technicians they trust could ...
(Date:11/30/2015)... ... November 30, 2015 , ... The Museum of Science & ... a new era of publicly accessible automated technology. Now, by popular demand, the ... guests an up-close look at the shuttle at MOSI’s main entrance. This experience ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... -- IBA Molecular North America, Inc. (IBAMNA), a U.S. leader ... as of January 1, 2016, it will do business ... rebrand the company reflects a refined vision for the ... relationship with Zevacor Molecular.  Both IBAMNA and Zevacor Molecular ... Peter Burke , Vice President Sales and ...
(Date:11/30/2015)... -- North America was valued at ... a CAGR of 7.6% from 2015 to 2020. --> ... in 2014, and is expected to grow at a CAGR of ... new Market Research Report "North America Cardiac Output Monitoring Devices Market ... care, others) - Analysis And Forecast To 2020", the cardiac output ...
(Date:11/30/2015)... 30, 2015  Kevin Smith has been appointed ... global pioneer in wireless monitoring of vital signs.  ... , Mr. Smith will be responsible for ... strategy.  He will also directly oversee partnering with ... evidence for SensiumVitals, the first early warning detection ...
Breaking Medicine Technology: