Navigation Links
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."

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
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs surgery ... of Mohs Surgery and to Dr. Russell Peckham for medical and surgical dermatology. , ... for skin cancer. The selective fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey ...
(Date:6/25/2016)... Oklahoma City, Oklahoma (PRWEB) , ... June 25, ... ... to helping both athletes and non-athletes recover from injury. Recently, he has implemented ... for the Oklahoma City area —Johnson is one of the first doctors to ...
(Date:6/24/2016)... ... , ... June 19, 2016 is World Sickle Cell Observance Day. In an ... of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued a ... Cell Disease (SCD) is a disorder of the red blood cells, which can cause ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... Comfort Keepers® ... American Cancer Society and the Road To Recovery® program to drive cancer patients to ... and other adults to ensure the highest quality of life and ongoing independence. ...
(Date:6/24/2016)... Vegas, Nevada (PRWEB) , ... June 24, 2016 ... ... Las Vegas client, The Grove Investment Group (TGIG), has initiated cultivation and processing ... Grove, in Las Vegas and Pahrump, Nevada. , Puradigm is the manufacturer of ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016  Arkis BioSciences, a leading ... and more durable cerebrospinal fluid treatments, today announced ... Series-A funding is led by Innova Memphis, followed ... other private investors.  Arkis, new financing will accelerate ... the market release of its in-licensed Endexo® technology. ...
(Date:6/23/2016)... Any dentist who has made an implant supported ... Many of them do not even offer this as a ... laboratory costs involved. And those who ARE able to offer ... high cost that the majority of today,s patients would not ... Zadeh , founder of Dental Evolutions Inc. and inventor of ...
(Date:6/23/2016)... INDIANAPOLIS , June 23, 2016 Roche ... received 510(k) clearance for its Elecsys BRAHMS PCT (procalcitonin) ... severe sepsis or septic shock. With this clearance, Roche ... provide a fully integrated solution for sepsis risk assessment ... associated with bacterial infection and PCT levels in blood ...
Breaking Medicine Technology: