March 17, 2011 — (BRONX, NY) — Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered that members of an enzyme family found in humans and throughout the plant and animal kingdoms play a crucial role in regulating cell motility. Their findings suggest an entirely new strategy for treating conditions ranging from diabetic ulcers to metastatic cancer.
David Sharp, Ph.D., associate professor of physiology & biophysics, was the senior author of the study, which was published in the March 6 online edition of Nature Cell Biology.
"Cells in our bodies are in constant motion, migrating from their birth sites to distant targets," said Dr. Sharp. "Cellular movement builds our tissues and organs and underlies key functions such as the immune response and wound healing. But uncontrolled cell migration can lead to devastating problems including mental retardation, vascular disease and metastatic cancer."
Dr. Sharp and his colleagues found that certain members of an enzyme family known as katanin concentrate at the outer edge of non-dividing cells where they break up microtubules – dynamic intracellular polymers that regulate cell movement by controlling the formation of protrusions called lamellipodia. (Polymers are large molecules composed of many repeating units.)
When Dr. Sharp's team treated motile cells of the fruit fly Drosophila with a drug that inhibited katanin production, the treated cells moved significantly faster than control cells and with a striking increase in high-velocity movements, indicating that katanin prevents cells from moving too rapidly or in an uncontrolled manner. The researchers observed similar effects with katanin when they examined human cells.
"Our study opens up a new avenue for developing therapeutic agents for treating wounds – burns and diabetic ulcers, for example – as well as metastatic disease," added Dr. Sharp.
Describing katanin as a "microtubule regulator," Dr. Sharp said that its ability to modulate the speed and direction of cell movement – and not just control whether or not it occurs – could be especially useful from a clinical standpoint. Drugs that inhibit katanin, for example, could encourage cells to migrate in a particular direction to heal wounds. Conversely, he said, katanin itself or drugs that stimulate its production might be useful in treating or preventing cancer metastasis.
The title of the paper is "Drosophila katanin is a microtubule depolymerase that regulates cortical-microtubule plus-end interactions and cell migration." Other Einstein authors are Dong Zhang, Ph.D., Shannon Stewman, Ph.D., Emily Liebling, B.S., Uttama Rath, Ph.D., Tania Riera, B.S., Ana Asenjo, Ph.D., Hernando J. Sosa, Ph.D., and Ao Ma, Ph.D. Other authors include Kyle Grode, B.S., Joshua Currie, B.S., and Stephen Rogers, Ph.D., of the University of North Carolina, Chapel Hill, NC; Juan Daniel Diaz-Valencia, Ph.D., and Jennifer Ross, Ph.D., of the University of Massachusetts, Amherst, MA; and Daniel W. Buster, Ph.D., of the University of Arizona, Tucson, AZ.
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2009-2010 academic year, Einstein is home to 722 M.D. students, 243 Ph.D.students, 128 students in the combined M.D./Ph.D. program, and approximately 350 postdoctoral research fellows. The College of Medicine has 2,775 fulltime faculty members located on the main campus and at its clinical affiliates. In 2009, Einstein received more than $155 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five medical centers in the Bronx, Manhattan and Long Island - which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein - the College of Medicine runs one of the largest post-graduate medical training programs in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.einstein.yu.edu
Journal
Nature Cell Biology