Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lung cancer cells' survival gene seen as drug target

03.01.2008
One of the deadliest forms of cancer appears to carry a specific weakness.

When a key gene called 14-3-3zeta is silenced, lung cancer cells can't survive on their own, researchers have found.

The gene is a potential target for selective anti-cancer drugs, says Haian Fu, PhD, professor of pharmacology, hematology & oncology at Emory University School of Medicine and Emory Winship Cancer Institute.

The research results will be published the week of Dec. 24 in the Proceedings of the National Academy of Sciences (PNAS). The paper's first author is Zenggang Li, PhD, a postdoctoral fellow in Dr. Fu's laboratory.

Lung cancer kills more Americans annually than any other type of malignancy, according to the National Cancer Institute. Yet treatment options are very limited, Dr. Fu says.

"The recent trend towards targeted therapies requires us to understand the altered signaling pathways in the cell that allow cancer to develop," he says. "If you think about genes that are dysregulated in cancer as drivers or passengers, we want to find the drivers and then, aim for these drivers during drug discovery."

Dr. Fu and his collaborator, Fadlo Khuri, MD, deputy director of clinical and translational research at Emory Winship Cancer Institute, chose to focus on the gene 14-3-3zeta because it is activated in many lung tumors. In addition, recent research elsewhere shows that survival of lung cancer patients is worse if the gene is on overdrive in their tumors, Dr. Fu says.

14-3-3 genes are found in mammals, plants and fungi. In the human body, they come in seven flavors, each given a Greek letter. Scientists describe the proteins they encode as adaptors that clamp onto other proteins. The clamping function depends on whether the target protein is phosphorylated, a chemical switch that regulates processes such as cell division, growth, or death.

"We knew that 14-3-3 is important in controlling EGFR (epidermal growth factor receptor) signaling, which is a main pathway driving lung cancer," Dr. Fu says. A couple of recently introduced drugs that were shown to be effective against lung cancer target EGFR, he adds.

In the PNAS study, the authors used a technique called RNA interference to selectively silence the 14-3-3zeta gene. They found that when 14-3-3zeta is turned off, lung cancer cells become less able to form new tumor colonies in a laboratory test.

One of the most important properties of cancer cells is their ability to grow and survive without touching other cells or the polymers that connect them. While the authors found that the cells with 14-3-3zeta turned off do not grow more slowly, the cells are vulnerable to anoikis (Greek for homelessness), a form of cell death that happens when non-cancerous cells that are accustomed to growing in layers find themselves alone.

Further experiments showed that 14-3-3zeta regulates a set of proteins called the Bcl2 family that control programmed cell death, and its absence upsets the balance within the family.

"You can see how control of anoikis means 14-3-3zeta could play a critical role in cancer invasion and metastasis," Dr. Fu says. "The mechanistic question we still haven't answered is: what makes zeta unique so that it can't be replaced by the others."

The finding has implications beyond lung cancer, in that 14-3-3zeta is also activated in other forms of cancer such as breast and oral, he notes.

"Dr. Fu and his team's findings unmask the role of 14-3-3 zeta in the survival advantage of lung cancer cells and their dependence on it," Dr. Khuri says. "Targeting this critical molecule could lead to meaningful therapeutic progress."

Since 14-3-3zeta was identified as a promising target for drugs, Dr. Fu and his co-workers are making use of a robot-driven screening program at the Emory Chemical Biology Discovery Center to sort through thousands of chemicals that may disrupt its interactions specifically.

They hope to identify these compounds rapidly and move them from bench into clinic testing to benefit patients.

Vince Dollard | EurekAlert!
Further information:
http://www.emoryhealthcare.org

Further reports about: 14-3-3zeta Target cancer cells lung cancer survival

More articles from Life Sciences:

nachricht Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>