Researchers at Fox Chase Cancer Center have demonstrated that a protein called NEDD9 may be required for some of the most aggressive forms of breast cancer to grow. Their findings, based on the study of a mouse model of breast cancer, are presented in a recent issue of Cancer Research, available on-line now.
“For the first time, we have been able to present evidence that directly demonstrates reduced levels of NEDD9 in a living animal that limit the appearance of aggressive metastatic breast cancer,” says co-author Erica A. Golemis, PhD, Fox Chase professor and co-leader of the Molecular Translational Medicine Program.
According to Golemis, the protein could serve as a biomarker, a molecule that could be detected to indicate the diagnoses of aggressive forms of breast cancer in the clinic. NEDD9 may also provide a target for some future therapeutic against metastatic cancer, Golemis says.
In 1996, the Golemis laboratory first identified NEDD9, a so-called scaffolding protein that forms part of a complex of molecules just inside the cell membrane. NEDD9 and related proteins collectively act as transmitters, relaying signals from the cell surface to the cell interior to control cancer cell growth and movement. Over the past three years, scientists from laboratories around the world have contributed to a body of evidence showing how excess amounts of the NEDD9 contribute to metastasis in a number of cancers, including melanoma, lung cancer, and glioblastoma.
“One thought is that producing excess NEDD9 gives tumors a selective advantage over other cells,” Golemis says, “so we are trying to determine how NEDD9 might provide that advantage.”
To better understand the role of NEDD9 in breast cancer, the Fox Chase researchers studied a variety of mice, bred by colleagues at the University of Tokyo to lack the NEDD9 gene. These NEDD9 “knockout” mice were then made to turn on an oncogene that induces breast cancer in mice, and compared to normal mice given the same treatment. While the NEDD9 knockout mice developed breast cancers, they did so more slowly and less efficiently than normal mice, and without the activation of the central protein pathways most responsible for cancer growth and metastasis. In fact, mammary tumor growth in the knockout mice showed marked genetic differences from the very moment premalignant lesions were detected, as compared to the normal mice.
“This was the first study able to address the question of what happens in breast cancer if this gene isn't around,” Golemis says. “And the answer is that we see a more moderate cancer development, which alone speaks volumes on the role of the protein in aggressive breast tumors.”
According to Golemis, the emerging body of research on NEDD9 shows that the protein forms an important node in the complex, interwoven pathways that dictate the fate of individual cells. These pathways regulate the entirety of a cell's life, from how select genes are transcribed to form new proteins to how a cell divides or even dies.
“By their nature, cancer cells are evolutionary machines, constantly looking for ways to exploit these vast networks of protein signaling pathways that are an inherent part of cell function,” Golemis says. “The more we understand these pathways, the better we will understand the ways cancer cells evolve to use those pathways, and how to stop them.”
Co-authors in this study include Fox Chase researchers Eugene Izumchenko, Ph.D. Mahendra K. Singh, Ph.D., Ilya G. Serebriiski, Ph.D., Richard Hardy, Ph.D., Joy L. Little, Ph.D., Andres Klein-Szanto, M.D., Denise C. Connolly, PhD, Olga V. Plotnikova, and Nadezhda Tikhymanova.
Funding for this research comes from grants from the National Cancer Institute, National Institute for Health, Israel Cancer Association, Stanley Abersur Research Foundation, Ben-Gurion University of the Negev, Pew Charitable Fund, and the Commonwealth of Pennsylvania.
Fox Chase Cancer Center is one of the leading cancer research and treatments centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center's nursing program has received the Magnet status for excellence three consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX-CHASE or 1-888-369-2427.
Greg Lester | EurekAlert!
New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia
New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
21.08.2017 | Medical Engineering
21.08.2017 | Materials Sciences
21.08.2017 | Life Sciences