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 IU-led study reveals new insights into light color sensing and transfer of genetic traits
06.05.2016 | Indiana University

nachricht Thievish hoverfly steals prey from carnivorous sundews
06.05.2016 | Staatliche Naturwissenschaftliche Sammlungen Bayerns

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nuclear Pores Captured on Film

Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.

Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Expanding tropics pushing high altitude clouds towards poles, NASA study finds

06.05.2016 | Earth Sciences

IU-led study reveals new insights into light color sensing and transfer of genetic traits

06.05.2016 | Life Sciences

Thievish hoverfly steals prey from carnivorous sundews

06.05.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>