Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Fox Chase Researchers Discover Novel Role of the NEDD9 Gene in Early Stages of Breast Cancer

Breast cancer is the second leading cause of cancer deaths among women in the United States. Many of these deaths occur when there is an initial diagnosis of invasive or metastatic disease.

A protein called NEDD9—which regulates cell migration, division and survival—has been linked to tumor invasion and metastasis in a variety of cancers. Researchers at Fox Chase Cancer Center have now shown that NEDD9 plays a surprising role in the early stages of breast tumor development by controlling the growth of progenitor cells that give rise to tumors.

The findings, published in the journal Oncogene on January 14, 2013, could lead to personalized treatment strategies for women with breast cancer based on the levels of NEDD9 in their tumors.

"For several years, NEDD9 has been linked to tumor metastasis and invasion at later stages. This is the first study that really shows how important NEDD9 can be for the initiation of tumors in breast cancer, and to link this initiation process to progenitor cells," says lead study author Joy Little, PhD, a postdoctoral fellow at Fox Chase who works in the laboratory of senior study investigator Erica A. Golemis, PhD, Deputy Chief Scientific Officer and Vice President at Fox Chase.

In the study, Little, Golemis and their collaborators mated mice without the NEDD9 gene to mice engineered to develop HER2+ mammary tumors and unexpectedly found that these mice were largely resistant to tumor formation. Only 18% of the mice developed mammary tumors, compared with 80% of mice that had a functional NEDD9 gene. In contrast to previous research findings showing that an increase in NEDD9 levels promotes tumor aggressiveness, the researchers found that loss of NEDD9 had little effect on tumor metastasis, indicating that it is not required for this process in this specific context. Once formed, the tumors in mice lacking NEDD9 grew rapidly, suggesting that it either plays a less important role at later stages of tumor growth or tumors undergo compensatory changes that allow them to bypass the need for NEDD9.

Importantly, mice lacking NEDD9 showed a significant reduction in progenitor cell populations in the mammary gland compared with mice that had a functional NEDD9 gene. Progenitor cells from NEDD9-null mice were less likely to form three-dimensional mammospheres in culture, but proliferated at the same rate as cells from control mice. The loss of Nedd9 also made progenitor cells more sensitive to lower doses of two tumor-inhibiting drugs—a Food and Drug Administration-approved Src inhibitor called dasatinib, and a focal adhesion kinase inhibitor from a class of drugs currently being tested in clinical trials for the treatment of cancer. These findings suggest that these types of drugs would more effectively control breast cancer tumors with low levels of NEDD9.

"Eventually, with a biopsy, you may be able to get a read-out of all the mutations that a tumor has, and each one would potentially dictate whether or not a certain line of therapy would work for a specific tumor," Little says. "If NEDD9 levels are higher in a particular tumor, we could potentially determine whether or not it would be more sensitive to specific inhibitors."

To follow up on this work, the researchers plan to determine the mechanisms by which NEDD9 controls tumor formation, and examine whether NEDD9 plays a similar role in early stages of other types of cancer.

Co-authors on the study include Victoria Serzhanova, Eugene Izumchenko, Brian L. Egleston, Andres J. Klein-Szanto, and Maria Shubina of Fox Chase; Erica Parise of the University of Pittsburgh; Grace Loudon of Bryn Mawr College; Sachiko Seo and Mineo Kurokawa of the University of Tokyo; and Michael F. Ochs of Johns Hopkins University.

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 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.

Diana Quattrone | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>