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!
The herbivore dilemma: How corn plants fights off simultaneous attacks
09.02.2016 | Boyce Thompson Institute for Plant Research
Shedding Light on Bacteria
09.02.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau
Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels
A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...
Indications of light-induced lossless electricity transmission in fullerenes contribute to the search for superconducting materials for practical applications.
Superconductors have long been confined to niche applications, due to the fact that the highest temperature at which even the best of these materials becomes...
Researchers at King’s College London and the Wellcome Trust Sanger Institute in the United Kingdom have for the first time demonstrated a direct link between the Wbp2 gene and progressive hearing loss. The scientists report that the loss of Wbp2 expression leads to progressive high-frequency hearing loss in mouse as well as in two clinical cases of children with deafness with no other obvious features. The results are published in EMBO Molecular Medicine.
The scientists have shown that hearing impairment is linked to hormonal signalling rather than to hair cell degeneration. Wbp2 is known as a transcriptional...
Pollens, the bane of allergy sufferers, could represent a boon for battery makers: Recent research has suggested their potential use as anodes in lithium-ion batteries.
"Our findings have demonstrated that renewable pollens could produce carbon architectures for anode applications in energy storage devices," said Vilas Pol, an...
Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...
09.02.2016 | Event News
02.02.2016 | Event News
26.01.2016 | Event News
09.02.2016 | Event News
09.02.2016 | Materials Sciences
09.02.2016 | Power and Electrical Engineering