In an article published in the June issue of Nature, VCU Massey scientists Sarah Spiegel, Ph.D., and Tomasz Kordula, Ph.D., and their co-authors examine how sphingosine-1-phosphate (S1P), a lipid mediator in the blood that influences immune cell circulation, also regulates inflammation and cancer. They reported that S1P is a missing cofactor that is required for the activity of TRAF2, the key regulator of NF-kappaB, which acts as a master on-off switch in controlling inflammation and cancer.
Spiegel, who is internationally recognized for her pioneering work on bioactive lipid signaling, discovered almost two decades ago that S1P is a potent lipid mediator that stimulates cell growth. S1P and the kinase that produces it, SphK1, have since emerged as critical regulators of numerous fundamental biological processes affecting health and disease.
“It is difficult to find an area of physiology and pathophysiology in which S1P does not have important if not key roles. Appropriate to its name, which is associated with the enigma of the Sphinx, how S1P so profoundly regulates cell fate decisions has long remained a mystery,” said Spiegel, co-leader of VCU Massey’s Cancer Cell Signaling Program and chair of VCU School of Medicine’s Biochemistry and Molecular Biology Department.
The puzzle of how such a simple molecule as S1P can have diverse roles has been solved by VCU Massey researchers’ discovery that this lipid mediator functions not only as a “first messenger,” a ligand or agonist that binds to specific cell surface receptors, but also inside the cells as an “intracellular second messenger” that is required for activation of the transcription factor NF-kappaB.
These findings also provide an explanation for the numerous observations of the importance of the enzyme that produces S1P, SphK1, in protection of cancer cells against chemotherapeutic drugs and the correlation of its levels with poor prognosis of many types of cancers, including breast, colorectal and brain.
Spiegel hopes that specific SphK1 inhibitors they are developing will pave the way for future potent and specific drugs that target SphK1 for the treatment of cancer.
Spiegel and Kordula collaborated with researchers Sergio E. Alvarez, Ph.D.; Harikumar B. Kuzhuvelil; Ph.D.; Nitai C. Hait, Ph.D.; Jeremy Allegood, Ph.D.; Graham M. Strub, M.D./Ph.D. student; Eugene Y. Kim, Ph.D.; Michael Maceyka, Ph.D.; and Sheldon Milstien, Ph.D. – all from VCU Massey Cancer Center and the VCU School of Medicine’s Biochemistry and Molecular Biology Department – as well as Hualiang Jiang, Ph.D., and Cheng Luo, Ph.D., of the State Key Laboratory of Drug Research at Shanghai Institute of Materia Medica at Chinese Academy of Sciences.
View the full article at http://www.nature.com/nature/journal/v465/n7301/abs/nature09128.html.About the VCU Massey Cancer Center
Jenny Owen | EurekAlert!
Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center
Study advances gene therapy for glaucoma
17.01.2018 | University of Wisconsin-Madison
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
18.01.2018 | Earth Sciences
18.01.2018 | Business and Finance
18.01.2018 | Medical Engineering