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!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences