Researchers from Fox Chase Cancer Center have shown that NEDD9, a scaffolding protein responsible for regulating signaling pathways in the cell, promotes the growth and spread of epithelial ovarian cancer.
Previous studies have demonstrated the protein's importance in tumor invasion and spread of some lymphomas and many solid tumor types, including melanoma, neuroblastoma, and breast cancer, but its role in gynecological cancers has been poorly understood. The new data, to be presented on Sunday, April 6 at the AACR Annual Meeting 2014, suggest the protein activates known oncogenic signaling pathways in cancer cells, encouraging metastases.
"NEDD9 expression is usually associated with metastasis," says lead author Rashid Gabbasov, a graduate student in Fox Chase's Developmental Therapeutics Research Program and a researcher in the laboratory of Fox Chase Associate Professor Denise C. Connolly, PhD. "We've shown in two mouse models that expression of the protein probably plays an important role both in the initial development of ovarian cancer and tumor dissemination."
Because it lacks catalytic activity that might be inhibited, NEDD9 (neural precursor cell expressed, developmentally downregulated 9) itself is unlikely to be a suitable candidate for targeted therapy, says Gabbasov, and because it's not present in the blood it may not be suitable for diagnosing ovarian cancer. However, because the protein serves as a scaffolding molecule for other signaling proteins that play significant roles in cancer development and is important in several molecular pathways, it can inform future investigations of the biology of ovarian cancer in human cancer specimens. Researchers can investigate pathways downstream of the protein that are active in ovarian cancer to identify those which may be used as potential diagnostic or therapeutic biomarkers.
Epithelial ovarian cancer is diagnosed in more than 22,000 women every year. The disease kills about 14,000, according to the American Cancer Society. It is the fifth leading cause of cancer death in women and one of the most common gynecologic cancers. In most patients, the disease has already metastasized at the time of diagnosis.
Connolly, whose research focuses on understanding the molecular underpinnings of epithelial ovarian cancer, says she and her colleagues became interested in NEDD9 after learning about its role in other cancers. The protein was discovered in 1996 by Fox Chase Professor Erica A. Golemis, PhD, Co-Leader of the Center's Developmental Therapeutics Research Program and a co-author on the ovarian cancer study.
Proteins like NEDD9 control and regulate the signaling mechanisms between the surface and interior of a cell.
"At the time our research started, we saw an early report suggesting that high-level NEDD9 expression was part of a gene signature related to advanced stage ovarian cancer," says Connolly, senior author on the study.
To study the protein's role in epithelial ovarian cancer, Gabbasov and his colleagues compared tumor growth in two groups of mice bred to spontaneously develop ovarian tumors. Mice in one group lacked NEDD9, and mice in the other group expressed the protein. Using MRI scans, the researchers observed delayed tumor development in the NEDD9-null mice, compared to mice that expressed NEDD9. Analysis of tumor tissue showed more activity in several well-known oncogenic signaling pathways in the mice expressing the protein.
"When we compared the gene expression in these tumors, we were able to see how NEDD9 depletion really affects overall gene expression," says Gabbasov. "It really does affect numerous genes, and we will try to pursue these gene products to better understand the role of NEDD9."
Connolly says that even though this study looked at the ovarian cancer in mice, some of the genes that turned up in the gene expression analysis can be further evaluated in human cell lines and tumors. "We want to make sure we're studying something that's not only important in mice but can also give us clues about human cancers."
In addition to Gabbasov, Connolly and Golemis, coauthors of the study include Fox Chase Cancer Center researchers Laura E. Bickel, Shane W. O'Brien, and Samuel Litwin, as well as Sachiko Seo from the University of Tokyo in Japan, who developed the NEDD9 null mice.
Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment 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 four 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, visit Fox Chase's Web site at http://www.foxchase.org or call 1-888-FOX CHASE or (1-888-369-2427).
Diana Quattrone | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy