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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>