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 Pathogenic bacteria hitchhiking to North and Baltic Seas?
22.07.2016 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Unconventional quasiparticles predicted in conventional crystals
22.07.2016 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

Im Focus: A Peek into the “Birthing Room” of Ribosomes

Scaffolding and specialised workers help with the delivery – Heidelberg biochemists gain new insights into biogenesis

A type of scaffolding on which specialised workers ply their trade helps in the manufacturing process of the two subunits from which the ribosome – the protein...

Im Focus: New protocol enables analysis of metabolic products from fixed tissues

Scientists at the Helmholtz Zentrum München have developed a new mass spectrometry imaging method which, for the first time, makes it possible to analyze hundreds of metabolites in fixed tissue samples. Their findings, published in the journal Nature Protocols, explain the new access to metabolic information, which will offer previously unexploited potential for tissue-based research and molecular diagnostics.

In biomedical research, working with tissue samples is indispensable because it permits insights into the biological reality of patients, for example, in...

Im Focus: Computer Simulation Renders Transient Chemical Structures Visible

Chemists at the University of Basel have succeeded in using computer simulations to elucidate transient structures in proteins. In the journal Angewandte Chemie, the researchers set out how computer simulations of details at the atomic level can be used to understand proteins’ modes of action.

Using computational chemistry, it is possible to characterize the motion of individual atoms of a molecule. Today, the latest simulation techniques allow...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

Partner countries of FAIR accelerator meet in Darmstadt and approve developments

11.07.2016 | Event News

 
Latest News

Hey robot, shimmy like a centipede

22.07.2016 | Information Technology

New record in materials research: 1 terapascals in a laboratory

22.07.2016 | Physics and Astronomy

University of Graz researchers challenge 140-year-old paradigm of lichen symbiosis

22.07.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>