Fox Chase Cancer Center LogoA novel research from Fox Chase Cancer Center provides evidence that absence of a protein called NEDD9 protein seems to limit breast cancer. Also, NEDD9 could perhaps serve as an indicator for aggressive forms of the disease. Researchers are believed to have demonstrated that the protein may be required for some of the most aggressive forms of breast cancer to grow.

In 1996, the Golemis laboratory was believed to have first identified NEDD9. NEDD9 is known to be a so-called scaffolding protein which forms part of complex molecules simply inside the cell membrane. It was observed that NEDD9 and related proteins together act as transmitters thereby spreading signals from the cell surface to the cell interior in order to control cancer cell growth and movement.

Over the past three years, scientists from laboratories around the world have added to a body of evidence showing how excess amounts of the NEDD9 seem to contribute to metastasis in a number of cancers. Apparently, these cancers include melanoma, lung cancer, and glioblastoma.

Co-researcher Erica A. Golemis, PhD, Fox Chase professor and co-leader of the Molecular Translational Medicine Program stated that, “For the first time, we have been able to present evidence that directly demonstrates reduced levels of NEDD9 in a living animal that limit the appearance of aggressive metastatic breast cancer.”

Golemis was of the opinion that the protein may possibly serve as a biomarker thereby indicating the diagnoses of aggressive forms of breast cancer in the clinic. Moreover, NEDD9 may provide a target for some potential therapeutic against metastatic cancer.

“One thought is that producing excess NEDD9 gives tumors a selective advantage over other cells. So we are trying to determine how NEDD9 might provide that advantage,” adds Golemis.

For the purpose of better understanding the role of NEDD9 in breast cancer, the Fox Chase researchers studied a variety of mice which were bred by colleagues at the University of Tokyo in order to be deficient in the NEDD9 gene.

These NEDD9 ‘knockout’ mice were then made to turn on an oncogene which induces breast cancer in mice. These mice were then compared to normal mice which were given the same treatment.

Golemis further elucidated, “This was the first study able to address the question of what happens in breast cancer if this gene isn’t around. And the answer is that we see a more moderate cancer development, which alone speaks volumes on the role of the protein in aggressive breast tumors.”

“By their nature, cancer cells are evolutionary machines, constantly looking for ways to exploit these vast networks of protein signaling pathways that are an inherent part of cell function. The more we understand these pathways, the better we will understand the ways cancer cells evolve to use those pathways, and how to stop them,” continues Golemis.

The findings revealed that though the NEDD9 knockout mice seemed to have developed breast cancers, they did so more slowly and less efficiently in contrast to normal mice. However, it occurred without the activation of the central protein pathways which were most responsible for cancer growth and metastasis.

In fact, mammary tumor growth in the knockout mice seemed to have shown marked genetic differences from the very moment premalignant lesions were detected as compared to the normal mice.

According to Golemis, the emerging body of research on NEDD9 shows that the protein forms an important node in the complex, interwoven pathways which seem to dictate the fate of individual cells. Allegedly, these pathways control the total life of a cell, from how select genes are transcribed to form novel proteins to how a cell divides or even dies.

The findings of the research have been published in the journal, Cancer Research.