Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research may explain how foremost anticancer 'guardian' protein learned to switch sides

30.07.2014

Researchers at Cold Spring Harbor Laboratory (CSHL) have discovered a new function of the body's most important tumor-suppressing protein.

Called p53, this protein has been called "the guardian of the genome." It normally comes to the fore when healthy cells sense damage to their DNA caused by stress, such as exposure to toxic chemicals or intense exposure to the sun's UV rays.


The protein p53-psi, a variant of the well-known anti-cancer guardian protein p53, can reprogram cells to "switch sides" and acquire pro-metastatic features. Pro-metastatic cells naturally expressing p53-psi are seen in LEFT panel. On RIGHT, when p53-psi is silenced, these cells reacquire the characteristics of non-metastatic cells.

Credit: Sordella lab, Cold Spring Harbor Laboratory


The protein p53-psi, a variant of the well-known anti-cancer guardian protein p53, can reprogram cells to "switch sides" and acquire pro-metastatic features. Two types of cells that don't naturally express p53-psi (LEFT panel) exhibit changes in shape (RIGHT panel) characteristic of the transition to metastasis when they are made to express p53-psi.

Credit: Sordella lab, Cold Spring Harbor Laboratory

If the damage is severe, p53 can cause a cell to commit preprogrammed cell-death, or apoptosis. Mutant versions of p53 that no longer perform this vital function, on the other hand, are enablers of many different cancers.

Cancer researcher Dr. Raffaella Sordella, a CSHL Associate Professor, and colleagues, today report in Proceedings of the National Academy of Sciences the discovery of a p53 cousin they call p53-psi (the Greek letter "psi"). It is a previously unknown variant of the p53 protein, generated by the same gene, called TP53 in humans, that gives rise to other forms of p53.

Sordella and colleagues observed that p53-psi, when expressed, reduces the expression of a molecular glue called E-cadherin, which normally keeps cells in contact within epithelial tissue, the tissue that forms the lining of the lung and many other body organs.

This is accompanied by expression of key cellular markers associated with tumor invasiveness and metastatic potential. (These are markers of EMT, or epithelial-to-mesenchymal transition.) Consistently, Sordella and her team found levels of p53-psi to be elevated in early-stage lung tumors with poor prognosis.

Careful investigation revealed that p53-psi generates pro-growth effects by interacting with a protein called cyclophillin D (CypD), at the membrane of the cell's energy factories, the mitochondria, and by spurring the generation of oxidizing molecules called reactive oxygen species (ROS).

p53-psi was found by the team to be inherently expressed in tumors but also in injured tissue. "This is intriguing," Sordella says, "because generation of cells bearing characteristics of those seen in wound healing has been seen previously, in tumors."

It is possible, Sordella says, that more familiar p53 mutants associated with tumor growth and metastasis may have "hijacked" those abilities from the program used by p53-psi; to promote healing during tissue injury. A cellular program, in other words, that evolved over eons to heal may have been hijacked by mutant p53 to enable cancers to spread out of control.

The team is currently investigating p53-psi in wound healing to help clarify its role. Confirmation would lend support to the theory that mutant p53 hijacks that function to help advance pro-metastatic processes in cancer.

###

The research discussed in this release was funded by a grant from the Damon Runyon Cancer Research Foundation.

"p53-psi is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state" appears online ahead of print the week of July 28, 2014 in Proceedings of the National Academy of Sciences. The authors are: Serif Senturk, Zhan Yao, Matthew Camiolo, Brendon Stiles, Trushar Rathod, Alice M. Walsh, Alice Nemajerova, Matthew J. Lazzara, Nasser K. Altorki, Adrian Krainer, Ute M. Moll, Scott W. Lowe, Luca Cartegni and Raffaella Sordella. The paper can be obtained at: http://www.pnas.org/content/early/recent

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for the impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 600 researchers and technicians strong and its Meetings & Courses program hosts more than 12,000 scientists from around the world each year to its Long Island campus and its China center. For more information, visit http://www.cshl.edu.

Peter Tarr | Eurek Alert!

Further reports about: CSHL Cancer Harbor Laboratory Sordella anticancer damage exposure function healing markers p53 tumors

More articles from Life Sciences:

nachricht Cells cling and spiral 'like vines' in first 3-D tissue scaffold for plants
27.08.2015 | University of Cambridge

nachricht Cellular contamination pathway for plutonium, other heavy elements, identified
27.08.2015 | DOE/Lawrence Berkeley National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: What would a tsunami in the Mediterranean look like?

A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).

Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...

Im Focus: Self-healing landscape: landslides after earthquake

In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.

These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...

Im Focus: FIC Proteins Send Bacteria Into Hibernation

Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.

For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...

Im Focus: Fraunhofer IPA develops prototype of intelligent care cart

It comes when called, bringing care utensils with it and recording how they are used: Fraunhofer IPA is developing an intelligent care cart that provides care staff with physical and informational support in their day-to-day work. The scientists at Fraunhofer IPA have now completed a first prototype. In doing so, they are continuing in their efforts to improve working conditions in the care sector and are developing solutions designed to address the challenges of demographic change.

Technical assistance systems can improve the difficult working conditions in residential nursing homes and hospitals by helping the staff in their work and...

Im Focus: A Grand Voyage for Tiny Organisms

Climate and Ecosystem Change in the Mediterranean

Since the opening of the Suez Canal in 1869 many hundreds of marine animal and plant species from the Red Sea have invaded the eastern Mediterranean, leading...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking conference in Heidelberg for outstanding mathematicians and computer scientists

20.08.2015 | Event News

Scientists meet in Münster for the world’s largest Chitin und Chitosan Conference

20.08.2015 | Event News

Large agribusiness management strategies

19.08.2015 | Event News

 
Latest News

Cells cling and spiral 'like vines' in first 3-D tissue scaffold for plants

27.08.2015 | Life Sciences

Hypoallergenic parks: Coming soon?

27.08.2015 | Health and Medicine

Stiffer breast tissue in obese women promotes tumors

27.08.2015 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>