Karin List, Ph.D., assistant professor of Pharmacology at the Wayne State University School of Medicine, has received a five year, $1,577,000 Research Project (RO1) Grant from the National Cancer Institute/National Institutes of Health to study the role of two proteases and their functions in breast cancer development and progression.
Proteases are cellular enzymes that cleave proteins. They play a role in cell movement, promote blood clotting and spur tissue development, among other activities. At elevated levels, they can lead to the development of cancer. Dr. List, who also serves as director of Transgenic Technology at the Barbara Ann Karmanos Cancer Institute, is studying the matriptase and prostasin proteases as potential therapeutic targets in the treatment of metastatic breast cancer.
The goal of the research is to determine the functional and mechanistic properties of matriptase in breast cancer in the laboratory and its effects on prostasin. Previous studies have shown that prostasin cleaves and is activated by matriptase. Based on those findings, Dr. List hypothesizes that matriptase plays an important role in breast cancer carcinogenesis and that matriptase-mediated activation of prostasin is a critical process involved in breast cancer progression.
"Short term, we want to learn if matriptase and prostasin play a critical role in breast cancer," Dr. List said. "We need to look at the basic mechanisms before developing an intervention. The ultimate goal is to test drugs that target these proteases in patients."
Dr. List has created the necessary laboratory models to test the hypothesis. Matriptase was identified as a protease in 1997, but since then it has been challenging to create the proper physiological testing environments in which to study the role of the protease as it relates to breast cancer. She also has studied matriptase's role in squamous cell carcinoma of the skin and has found that high levels of matriptase lead to the formation of malignant tumors. For that reason, matriptase, along with prostasin, may be novel targets for patients with breast or other kinds of cancer.
"We are honored to have the importance of our work recognized with this National Cancer Institute grant," Dr. List said. "I think it speaks to the potential high impact of this research project and the implications that targeting matriptase and prostasin may have on the future development of effective cancer therapies, not only for breast cancer but other cancers as well."
Research co-investigators include Julie Boerner, Ph.D., assistant professor of Oncology at the School of Medicine and Karmanos, and Judith Abrams, Ph.D., professor of Oncology at WSU and Karmanos. Other collaborators include Ben Margolis, M.D., of the University of Michigan; Alfredo Molinolo, M.D., Ph.D., of the National Institute of Dental and Craniofacial Research at the National Institutes of Health; and Bonnie Sloane, Ph.D., distinguished professor and chair of WSU Pharmacology.