Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scaffolding protein promotes growth and metastases of epithelial ovarian cancer

07.04.2014

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!

Further reports about: Golemis NEDD9 activity epithelial genes metastases ovarian pathways tumors

More articles from Life Sciences:

nachricht Great apes communicate cooperatively
25.05.2016 | Max-Planck-Institut für Ornithologie

nachricht Rice study decodes genetic circuitry for bacterial spore formation
24.05.2016 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

Im Focus: Transparent - Flexible - Printable: Key technologies for tomorrow’s displays

The trend-forward world of display technology relies on innovative materials and novel approaches to steadily advance the visual experience, for example through higher pixel densities, better contrast, larger formats or user-friendler design. Fraunhofer ISC’s newly developed materials for optics and electronics now broaden the application potential of next generation displays. Learn about lower cost-effective wet-chemical printing procedures and the new materials at the Fraunhofer ISC booth # 1021 in North Hall D during the SID International Symposium on Information Display held from 22 to 27 May 2016 at San Francisco’s Moscone Center.

Economical processing

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

LZH shows the potential of the laser for industrial manufacturing at the LASYS 2016

25.05.2016 | Trade Fair News

Great apes communicate cooperatively

25.05.2016 | Life Sciences

Thermo-Optical Measuring method (TOM) could save several million tons of CO2 in coal-fired plants

25.05.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>