Wnt proteins are a large family of proteins that active signaling pathways (a set of biological reactions in a cell) to control several vital steps in embryonic development. In adults, Wnt-mediated functions are frequently altered in many types of cancers and, specifically, within cell subpopulations that possess stem cell-like properties.
In two studies, one in the recent issue of the journal Molecular and Cellular Biology and a second, published earlier this year in Science Signaling, D'Souza-Schorey's laboratory reports on the importance of the protein "ARF6" in Wnt signaling.
The best documented role of Wnt is its triggering of the canonical (idealized or generalized) signaling pathway that leads to the stabilization of a protein called beta-catenin. This in turn leads to activation of various target genes that result in changes in a wide spectrum of cell behaviors.
"We have had a long standing interest in understanding the role of ARF6 in cell behavior," D'Souza-Schorey said. "ARF6 is an interesting molecule at the nexus of several important cell-signaling pathways. Our interest in this line of investigation has only been heightened by emerging reports from many labs that ARF6 activity is dramatically increased in several cancers. In our most recent study, we show how ARF6 can propagate Wnt signaling leading to proliferative phenotypes that are frequently seen in epithelial tumors (a growth of irregularly-shaped cells on the outer membrane of an organ or gland)."
In the paper published in Science Signaling, the laboratory collaborated with researchers at the University of Utah to document the importance of ARF6-regulated activation of canonical Wnt signaling in the spread of melanoma. The study showed that a small molecule that prevents ARF6 activation could stop tumor invasion and the spread of the cancer.
"The relevance of Wnt signaling in human cancers in manifest by the frequency with which this pathway is aberrantly activated across a wide range of malignancies," D'Souza-Schorey said. "Given the number of Wnts, Wnt signaling has been difficult to target therapeutically. It is important to note that while there are many mechanisms that drive aberrant Wnt/beta-catenin signaling in diverse cancers, these different mechanisms nearly always occur in a mutually exclusive manner. Thus, a better understanding of mechanisms involved in Wnt signaling transduction offers several target molecules for cancer drug development."
Notre Dame graduate students James Clancy, Oscar Pellon-Cardenas, Alanna Sedgwick and Henriette Uwimphuwe were co-authors on the two studies from D'Souza-Schorey's laboratory.
Crislyn D'Souza-Schorey | EurekAlert!
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Life Sciences
19.10.2017 | Interdisciplinary Research
19.10.2017 | Earth Sciences