It has been known for some time that mutations in the APC gene occur in more than 85 percent of all sporadic colon cancers. Now researchers at Huntsman Cancer Institute at the University of Utah demonstrate in a study featured today in Cell the mechanism by which mutation of the APC gene affects a cellular process known as DNA methylation. DNA methylation is a chemical modification made to DNA that plays an important role in dictating how DNA is read and interpreted by a cell.
The group, led by David Jones, Ph.D., and Bradley Cairns, Ph.D., have now linked loss of Apc with DNA demethylase, an enzyme system that erases DNA methylation. Studies using human tissues and zebarafish demonstrate that this system is highly active in tissues harboring mutated Apc and may provide an explanation for the previously known loss of DNA methylation seen in early stage tumors. The activity of the DNA demethylase appears to stall the normal development of intestinal cells, leaving them in a stem cell-like state. Normal development was restored upon inhibition of the DNA demethylase system. The experiments conducted by the group also demonstrated that the mechanistic connection between APC mutation and demethylation is conveyed through changes in the amount of retinoic acid (RA), an important regulatory compound derived from dietary vitamin A.
"We believe that clarification of the mechanism leading to demethylation will have broad implications for a variety of cancers. Our increased understanding of the mechanics connecting APC mutation and demethylation presents new opportunities for colon cancer intervention and may lead the way to developing a truly finely tuned approach to treatment," said Jones. Cairns added, "Since the mechanism of action of the demethylase can inherently create new mutations, misregulation of the system could underlie the occurrence of mutations in additional oncogenes. Its inhibition may therefore allow us to both prevent and treat certain cancers."
The mission of Huntsman Cancer Institute (HCI) at The University of Utah is to understand cancer from its beginnings, to use that knowledge in the creation and improvement of cancer treatments, to relieve the suffering of cancer patients, and to provide education about cancer risk, prevention, and care. HCI is a National Cancer Institute-Designated Cancer Center, which means that it meets the highest national standards for cancer care and research and receives support for its scientific endeavors. HCI is also a member of the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of the world's leading cancer centers that is dedicated to improving the quality and effectiveness of care provided to patients with cancer. For more information about HCI, please visit www.huntsmancancer.org.
Linda Aagard | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy