Protein that supports breast cancer growth identified

Fox Chase Cancer Center researchers have demonstrated that a protein may be required for some of the most aggressive forms of breast cancer to grow.

The findings, based on the study of a mouse model of breast cancer, have been presented in a recent issue of Cancer Research.

“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,” says co-author Erica A Golemis, PhD, Fox Chase professor and co-leader of the Molecular Translational Medicine Program.

According to Golemis, the protein could serve as a biomarker, a molecule that could be detected to indicate the diagnoses of aggressive forms of breast cancer in the clinic.

NEDD9 may also provide a target for some future therapeutic against metastatic cancer, Golemis says.

In 1996, the Golemis laboratory first identified NEDD9, a so-called scaffolding protein that forms part of a complex of molecules just inside the cell membrane. NEDD9 and related proteins collectively act as transmitters, relaying signals from the cell surface to the cell interior to control cancer cell growth and movement. Over the past three years, scientists from laboratories around the world have contributed to a body of evidence showing how excess amounts of the NEDD9 contribute to metastasis in a number of cancers, including melanoma, lung cancer, and glioblastoma.

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

To better understand the role of NEDD9 in breast cancer, the Fox Chase researchers studied a variety of mice, bred by colleagues at the University of Tokyo to lack the NEDD9 gene. These NEDD9 “knockout” mice were then made to turn on an oncogene that induces breast cancer in mice, and compared to normal mice given the same treatment.

While the NEDD9 knockout mice developed breast cancers, they did so more slowly and less efficiently than normal mice, and without the activation of the central protein pathways most responsible for cancer growth and metastasis.

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