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 Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Nonstop Tranport of Cargo in Nanomachines

20.11.2018 | Life Sciences

Researchers find social cultures in chimpanzees

20.11.2018 | Life Sciences

When AI and optoelectronics meet: Researchers take control of light properties

20.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>