Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

By amplifying cell death signals, scientists make precancerous cells self-destruct

19.08.2008
When a cell begins to multiply in a dangerously abnormal way, a series of death signals trigger it to self-destruct before it turns cancerous.

Now, in research to appear in the August 15 issue of Genes & Development, Rockefeller University scientists have figured out a way in mice to amplify the signals that tell these precancerous cells to die. The trick: Inactivating a protein that normally helps cells to avoid self-destruction.

The work, led by Hermann Steller, Strang Professor and head of the Laboratory of Apoptosis and Cancer Biology, is the first to reveal the mechanism by which a class of proteins called IAPs regulates cell death. By exposing the mechanism in a living animal, the finding also marks a breakthrough in the field and opens the door for developing a new class of drugs that could aid in cancer therapy and prevention.

“In a way, these mice are guiding clinical trials,” says Steller, who is also a Howard Hughes Medical Institute investigator. “We now can study how IAPs contribute to the development of cancer in a living animal and develop drugs to prevent or thwart the disease.”

IAP stands for “inhibitor of apoptosis protein,” and these proteins do exactly what their name implies. By inhibiting apoptosis, or programmed cell death, they keep cells alive by directly binding to executioner enzymes called caspases. But until now, precisely how IAPs save cells from death has remained unclear.

With graduate student Andrew Schile and postdoc Maria Garcia-Fernandez, Steller studied the X-linked inhibitor of apoptosis protein, or XIAP, and the role of its largely ignored RING domain, which has been implicated in promoting cell death as well as survival. Steller, Schile and Garcia-Fernandez found that genetically targeting and removing RING affected only some cell types in healthy mice. And even though the mice without the RING had more cell death than the mice with the RING, both lived normal lives under normal laboratory conditions.

But when the scientists compared mice that were genetically predisposed to developing cancer, they found that those without the RING lived twice as long as those with it.

“Cancer cells thrive by disabling the molecular machinery that tells sick cells to die,” says Steller. “By removing the RING, we wanted to see whether we would trick the machinery to turn back on. And that’s what happened. Cells die more readily, making it much more difficult for cancer to be established.”

Steller and his team specifically showed that the RING transfers molecular tags on caspases that label these enzymes for destruction. The more tags, the stronger the signal to save the cell from death. However, when the RING is removed, fewer molecular tags are transferred to caspases and often, the signal to save the cell from death is not strong enough. So, more cells die.

The game is not over. Several distinct IAP genes are known to exist, but which ones are important in the development of cancer has also stymied researchers. “We need to use genetics to sort out which individual IAPs contribute to tumors and which IAPS we need to target in order to cure cancer,” says Steller. “This was a very big step in understanding what role IAPs play in cancer, but it isn’t the last.”

Thania Benios | EurekAlert!
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>