'We hope this novel discovery may aid in developing new treatment protocols,' said lead Mauricio J. Reginato, PhD.
Philadelphia, PA (PRWEB) May 22, 2014
A study from the Department of Biochemistry and Molecular Biology at Drexel University College of Medicine offers a potential new therapy for difficult-to-treat breast cancers. A team of investigators discovered that targeting a specific enzyme can kill triple-negative breast cancer cells, but spare non-tumor cells as well. The study is currently available in the online edition of Molecular Cell.
“Breast cancer is the world’s leading cancer in women, and the triple-negative breast cancer subtype is the deadliest and most difficult to treat since there is no targeted therapy currently available,” said the study’s lead investigator Mauricio J. Reginato, PhD, associate professor in the Department of Biochemistry and Molecular Biology. “We hope this novel discovery may aid in developing new treatment protocols.”
The team discovered that O-GlcNAc transferase (OGT), an enzyme that adds sugars to a number of nuclear and cytosolic proteins, is essential for allowing cancer cells to switch to glycolysis for energy demands. OGT regulates degradation of the hypoxia-inducible factor 1 (HIF-1a), a critical driver of cancer cell metabolism. Importantly, the study shows that reducing levels of OGT or blocking OGT activity with a small molecule selectively induced metabolic stress and cell killing in cancer cells but not in non-cancer breast cells. By profiling hundreds of metabolites, the team discovered that blocking OGT in tumor cells reduces critical metabolites involved in energy production that feeds cancer growth and survival. The authors also discovered that one metabolite elevated under these conditions alpha-ketoglutarate, a critical cofactor for HIF-1a regulation and degradation, is one mechanism by which OGT regulates HIF-1a.
The team showed that this tumor subtype contains higher expression of OGT and HIF-1a compared to other breast cancer subtypes. These results provide evidence that targeting OGT in difficult-to-treat triple-negative breast cancer may provide a future therapeutic option.
The members of the research team included: lead author Christina Ferrer and Valeria Sodi, both PhD candidates in the Molecular and Cell Biology and Genetics program; medical student John Falcone; and former student Thomas Lynch, PhD. This research is supported by National Cancer Institute R01 and F31 grants, and past CURE grants. This work also included collaborators from the University of Tennessee and Simon Fraser University in Canada.
About Drexel University College of Medicine
Drexel University College of Medicine has established some of the most highly innovative and rigorous academic programs available today, incorporating the University’s expertise in engineering and technology into traditional medical training. The College of Medicine is home to one of the nation’s leading centers for spinal cord research; one of the foremost centers for malaria study; and a highly regarded HIV/AIDS program with extensive NIH-funded research in prevention and therapeutic interventions. Drexel University College of Medicine has been designated a Vanguard National Center of Excellence in Women’s Health by the U.S. Department of Health & Human Services, and is highly respected in numerous other specialties including cardiology and pain management. Visit http://www.drexelmed.edu for more information. Follow Drexel University College of Medicine on Facebook, YouTube, Twitter and Instagram.