Navigation Links
Molecular switch identified that controls key cellular process

New York, NY and Oxford, UK, August 1, 2012 The body has a built-in system known as autophagy, or 'self-eating,' that controls how cells live or die. Deregulation of autophagy is linked to the development of human diseases, including neural degeneration and cancer.

In a study published online this week in the Proceedings of the National Academy of Sciences, scientists at the Ludwig Institute for Cancer Research in Oxford discovered a critical molecular switch that regulates autophagy. They also studied the links between autophagy and a cellular process called senescence that stops cell growth permanently.

The researchers identified ASPP2, a tumor suppressor, as a molecular switch that can dictate the ability of a common cancer gene, known as the RAS oncogene, to either stop or promote senescence.

As Yihua Wang and researchers in Xin Lu's group at the Ludwig Institute investigated the life cycle of fibroblast cells the most common connective tissue cells in animals they found that reduced levels of the ASPP2 protein increase RAS oncogene-induced autophagic activity. This in turn prevented cells from entering senescence. Without ASPP2, the cells continued to proliferate unchecked, thereby promoting tumor growth.

ASPP2 is known to play a role in suppressing tumor development. Mice that have a deficiency or malfunction in this protein have a predisposition to developing tumors. And low ASPP2 levels in patients are linked to poor prognoses in cancers, such as large B-cell lymphomas. Reduced ASPP2 expression has also been observed in highly metastatic breast tumors. But until now, researchers did not understand why.

"We found that in the presence of the common cancer-causing RAS oncogene, ASPP2 interacted with a protein complex that is responsible for deciding cell fate via autophagy," said Yihua Wang, PhD, Ludwig researcher in Oxford.

"What this means is that the cell's emergency stop button is disabled when ASPP2 expression is reduced or lost, allowing it to proliferate unchecked as with cancer," added Wang.

"The balance between the RAS oncogene and ASPP2 activity is crucial to determining whether or not tumor growth is promoted. Our next step will be to identify ways to alter ASPP2 activity at that critical switch point. This could be an effective way to treat cancers with reduced ASPP2 expression and mutated RAS, such as breast and colon cancers," concluded Wang.

"Some of the recently developed anti-cancer drugs are potent inducers of autophagy. The new findings may also offer an explanation as to why patient response to these drugs can vary dramatically. There are factors at play within the body that can dictate authophagic activity and impact clinical outcomes," said Xin Lu, PhD, director of Ludwig's Oxford Branch. "While further study is needed, these findings may in the longer term help doctors to identify patients who are more likely to respond well to autophagic inhibition," added Lu.

Contact: Rachel Steinhardt
Ludwig Institute for Cancer Research

Related medicine news :

1. Researchers unveil molecular details of how bacteria propagate antibiotic resistance
2. Media alert: 24th EORTC - NCI - AACR Symposium Molecular Targets and Cancer Therapeutics
3. Better treatment for brain cancer revealed by new molecular insights
4. Grb2 holds powerful molecular signaling pathway in check
5. New molecular structure offers first picture of a protein family vital to human health
6. Scientists discover distinct molecular subtype of prostate cancer
7. Molecular subtypes and genetic alterations may determine response to lung cancer therapy
8. Small molecular bodyguards kill HPV-infected cancer cells by protecting tumor-suppressor
9. Molecular probes identify changes in fibronectin that may lead to disease
10. Coordinating the circadian clock: Molecular pair controls time-keeping and fat metabolism
11. Force of habit: Stress hormones switch off areas of the brain for goal-directed behaviour
Post Your Comments:
(Date:11/27/2015)... ... November 27, 2015 , ... ProSidebar: Fashion is a ... X. With ProSidebar: Fasion, video editors can easily add an informative sidebar to ... title opener. Utilize presets featuring self-animating drop zones, lines, bars, and text with ...
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... ... failing. Secura Consultants has prided itself for not only fulfilling the needs of ... protection solutions at an affordable price and providing top-tier customer service. However, there's ...
(Date:11/27/2015)... ... November 27, 2015 , ... Avid collector, Andrew Hawley ... Michigan boxing style concert posters. This is one of Joplin's most famous and beautiful ... at the University of Michigan in Ann Arbor. The According to Hawley, "It is ...
(Date:11/26/2015)... ... November 26, 2015 , ... ... Representative. As a franchise owner, Somu now offers travelers, value and care based ... packages, private cruise sales, as well as, cabin upgrades and special amenities such ...
(Date:11/26/2015)... ... November 26, 2015 , ... Pixel Film ... trailer titles with ProTrailer: Vintage. This newly styled ProTrailer pack comes with 30 ... with any font, giving users limitless opportunities to stylize and create designs quickly ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... 2015 Research and Markets ( ) ... Care Market by Type (Dressings, Therapy Devices, Active Wound ... Out-Patient Facility), and Geography - Global Forecast to 2020" ... --> --> The purpose of this ... of the global advanced wound care market. It involves ...
(Date:11/26/2015)... -- Research and Markets ( ) has ... Horizons and Growth Strategies in the Italian Therapeutic ... Forecasts, Competitive Intelligence, Emerging Opportunities" report to ... --> This new 247-page report provides ... monitoring market, including emerging tests, technologies, instrumentation, sales ...
(Date:11/25/2015)... SYDNEY , Nov. 26, 2015  The total global ... nearly 7% over 2015-2016. Latin America ... Asia , (excluding Japan ), is ... continues to face increased healthcare expenditure. In 2013-2014, ... expenditure declined from 43.5% in 2008-2009 to 41.2% in 2013-2014. ...
Breaking Medicine Technology: