February 20, 2012

For the first time, researchers at Drexel University College of Medicine have discovered that a certain type of sugar found naturally in the body is elevated in prostate cancer cells and it plays a critical role in cancer growth and movement. The findings are set to be published in the April edition of Journal of Biological Chemistry.

The research team previously identified a specific type of sugar that was elevated in breast cancer cells and which plays a critical role in the growth and spread of breast cancer. Now, this same research team has discovered that this same sugar is also elevated in prostate cancer and it also aids in multiplying and spreading the disease, which is the second leading cause of cancer-related death in the United States among men.

"This sugar, O-GlcNAc, is used inside cells to tag proteins and alter their function. Cancer cells become very dependent on this sugar for growth and spread," said the study's lead researcher Mauricio J. Reginato, PhD, associate professor in the Department of Biochemistry and Molecular Biology at Drexel University College of Medicine. "We've known for a long time that cancer cells are addicted to sugar. With the evidence that this sugar is elevated in both prostate and breast cancer development, we may, in the future, be able to develop ways to suppress this sugar, which could lead to more targeted treatment protocols for these types of cancer."

In the study, O-GlcNAc was found to be elevated in a panel of prostate cancer cell lines. Normalizing the levels of O-GlcNAc significantly reduced the invasive and angiogenic potential of such cells. The researchers have found that prostate cancer cells, with reduced levels of O-GlcNAc, had a significant reduction in the incidence of bone metastasis.

This study indicates that targeting the enzyme that adds this sugar to proteins could have therapeutic potential in the treatment of several types of cancers. O-GlcNAc transferase (OGT) is the single enzyme responsible for modifying proteins, and thereby altering protein function, interaction, stability or expression. Through the use of a first generation small molecule inhibitor that blocks the activity of OGT, the researchers were able to recreate the effects of lowering O-GlcNAc levels, indicating that targeting the activity of OGT in cancer cells is a potential therapeutic strategy for treating prostate cancers. Reginato and colleagues are now trying to identify more specific small molecule inhibitors of OGT that can be used as therapeutic agents against cancer spread.

This research was partially funded by grants from PA CURE and the National Institutes of Health.