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 Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)

nachricht Self-assembled nanostructures hit their target
23.09.2016 | King Abdullah University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Chains of nanogold – forged with atomic precision

23.09.2016 | Life Sciences

New leukemia treatment offers hope

23.09.2016 | Health and Medicine

Self-assembled nanostructures hit their target

23.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>