The findings, recently published in Journal of Clinical Investigation, provide the first example of a protein factor regulating the expression of the protein caspase-9, a main player in apoptosis, or programmed cell death. Scientists have known that healthy cells favor caspase-9a, a form of the caspase-9 protein that promotes natural apoptosis.
What Chalfant and his research team found is that NSCLC cells favor caspase-9b, which is the anti-apoptotic form of caspase-9 that promotes tumor formation, growth and maintenance. Their further investigation discovered that a protein known as hnRNP L functions as an RNA splicing factor by promoting the expression of caspase-9b through a process known as RNA splicing. While hnRNP L was previously known to have a role in protein expression, its function in relation to cancer biology was unclear until Chalfant's study.
"We're researching an unexplored area of RNA splicing factors in relation to cancer," says Chalfant. "Before this study, there had been very little evidence of an RNA splicing event that results in cancerous tumor development. This study points to caspase-9b as being a very important target in the development of a durable therapy for non-small cell lung cancer."
In mouse models, the researchers used a virus-based targeted gene therapy to reduce the amount of hnRNP L in NSCLC cells. They then observed a lower ratio of caspase-9b to caspase-9a. The result completely stopped the growth of the tumors and had no negative effects on healthy cells. This decrease in the cancer cells' capacity to maintain tumors could make them more susceptible to chemotherapy drugs that typically have little effect on NSCLC.
"Unfortunately, many current therapies for lung cancer are less effective and more toxic than we'd like," says Chalfant. "Lung cancer kills more people than any other cancer, and there is a real need for new cellular targets that are cancer-specific and show results in large numbers of patients regardless of the mutations found in individual tumors. Since caspase-9b is mainly expressed in malignant cells, these findings may provide innovative treatments for non-small cell lung cancer with little to no toxic side effects."
Chalfant collaborated on this work with Davis Massey, M.D., D.D.S., Ph.D., at VCU School of Medicine's Department of Pathology and with researchers at VCU School of Medicine's Department of Biochemistry and Molecular Biology and Department of Physiology, as well as with the University of Colorado Cancer Center; the University of Texas Southwestern Medical Center; and the Hunter Holmes McGuire Veterans Administration Medical Center.
The study was supported by grants from the Veteran's Administration, National Institutes of Health, National Cancer Institute, National Aeronautics and Space Agency and International Association for the Study of Lung Cancer as a Young Investigator Award.
The full research article is available at: http://www.jci.org/articles/view/43552/files/pdf.
About VCU Massey Cancer Center: VCU Massey Cancer Center is one of 66 National Cancer Institute-designated institutions that leads and shapes America's cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It has one of the largest offerings of cancer clinical trials in Virginia, serving patients in Richmond and in four satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at www.massey.vcu.edu or call 1-877-4-MASSEY.
About VCU and the VCU Medical Center
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls more than 32,000 students in 211 certificate and degree programs in the arts, sciences and humanities. Sixty-nine of the programs are unique in Virginia, many of them crossing the disciplines of VCU's 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation's leading academic medical centers.
John Wallace | EurekAlert!
Improving memory with magnets
28.03.2017 | McGill University
Graphene-based neural probes probe brain activity in high resolution
28.03.2017 | Graphene Flagship
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy