Researchers work with colleagues at NIH and in New Orleans and Taiwan
Oct. 2, 2012 — Working with several academic institutions from around the world, professors and students from the University of Louisiana at Monroe have discovered a way to control breast cancer behaviors, fight anticancer drug resistance, and help fend off tumor recurrence.
Ceramide Glycosylation by Glucosylceramide Synthase Selectively Maintains the Properties of Breast Cancer Stem Cells
Background: Glucosylceramide synthase catalyzes ceramide glycosylation that regulates the synthesis of glycosphingolipids.
Results: Increased globo-series glycosphingolipids in breast cancer stem cells activates cSrc signaling and β-catenin–mediated transcription up-regulating stem cell factors.
Conclusion: Ceramide glycosylation maintains the stemness of cancer stem cells.
Significance: Glycosphingolipids in cell membrane actively participate in maintaining cancer stem cells.
Two well-known journals, including The Journal of Biological Chemistry, published these findings in recent issues.
Researchers from Louisiana State University Health Sciences Center in Shreveport, Academia Sinica in Taiwan, Tulane University School of Medicine in New Orleans, Xavier University in New Orleans, and the National Cancer Institute in Bethesda, Md. all contributed to the success of the studies.
Dr. Yong-Yu Liu, associate professor in ULM’s College of Pharmacy, along with three ULM pharmacy Ph.D. students, Vineet Gupta, Kaustubh N. Bhinge, and Salman B. Hosain, and summer student Katherine Xiong, researched the properties and behaviors of breast cancer stem cells, finding new measures to control those cells — cells that have not always reacted in the way cancer researchers and doctors assumed.
“Cancer stem cells are malignant seeds that not only generate tumors, but also cause tumor recurrence,” said Liu.
“Critical questions that puzzle scientists are: why do tumors develop promptly after chemotherapy failure, and how can cancer stem cells be killed, without harming normal adult stem cells that are needed to maintain normal tissues?”
According to Liu, their findings show that the ceramide glycosylation, catalyzed by glucosylceramide synthase, selectively controls the tumor behaviors of breast cancer stem cells rather than normal stem cells, such as bone marrow stem cells.
Ceramide is a particular lipid generated after drug treatment that can kill cells, including cancer cells.
Glycosylation blocks ceramide-induced death of cancer stem cells. Moreover, the glycosylation allows for the generation of more cancer stem cells. With this glycosylation shield, cancer stem cells survive, and anticancer drugs kill normal stem cells, leading to side effects.
Liu continued, “These studies, for the first time, have answered researcher’s questions, and also indicate that controlling ceramide glycosylation has led to discovering new therapies, selectively killing breast cancer stem cells, and overcoming tumor resistance.”
The findings were the outcome of collaborative efforts, including those of ULM’s Dr. Seetharama Satyanarayana-Jois, associate professor in pharmacy, and Dr. Sharon Meyer, associate professor of toxicology.
“These findings are fundamental in determining not only cancer stem cell behavior, but also molecular targets for anticancer chemotherapy,” said Dr. Benny Blaylock, dean of The College of Pharmacy.
“Dr. Liu, his collaborators, and students have made a seminal observation in the field of cancer research. The College of Pharmacy is very proud to have such talented and dedicated researchers as part of our faculty.”
The research projects were funded by grants from the National Institute of General Medical Sciences and the Mizutani Foundation for Glycoscience.
Press release and photo of Dr. Liu courtesy of the University of Louisiana at Monroe. You can find the original press release here.