An enzyme found at elevated levels in several human cancers has been linked to abnormal tumor growth in fruit flies, a discovery that provides a new model for understanding the link between stem cell biology and cancer, according to researchers at the University of Oregon.
Using fluorescent staining and laser-scanning microscopy, the eight-member research team studied various mutations in a gene called aurora-A to observe how changes in protein expression affected the ability of Drosophila neuroblasts, a type of neural stem cell, to maintain their stem cell character without forming tumors.
Reporting in the Dec. 20 issue of the journal Genes & Development, Chris Doe and colleagues detail how an overproduction of renewed neuroblasts in the flies can be traced to misregulation by the aurora-A kinase. This enzyme under normal conditions appears to be critical as a traffic cop for various proteins during mitosis in neuroblasts, they concluded.
"In humans, there has been a lot of thought that maybe stem cell populations are at the heart of many cancers," said Ryan O. Andersen, a doctoral student in Doe's lab. "The numbers are off drastically. Instead of properly dividing, they are overproducing more stem cells rather than maintaining a steady population. This loss of regulation leads to tumors populated with these overproduced cells."
Andersen and Cheng-Yu Lee, a postdoctoral fellow, were lead authors on the paper. Doe, a Howard Hughes Medical Institute investigator, is a professor of biology in the UO Institute of Neuroscience and Institute of Molecular Biology.
In Drosophila, Doe's team found that a mutation in aurora-A, an evolutionary conserved gene in fruit flies and humans, results in two distinguishing problems: Proteins (Numb) involved in the differentiation into neurons and neuroblast self-renewal (aPKC) are not sorted to their proper sides of the cell, and the mitotic spindle that provides cortical polarity becomes misaligned. The subsequent splitting leads to new cells with improper proteins mixes, including an overproduction -- in this case 10 times more than normal -- of new neuroblasts that lead to tumors in the brain.
"We conclude that the aurora-A kinase is required to coordinate the position of proteins within the neuroblasts," Doe said. "When it is absent, too little neuron-promoting proteins are delivered into the young neurons and they never lose their stem-cell nature. This leads to a stem-cell tumor in the fly brain."
The team's findings appear to reverse traditional thinking that too much activation of aurora-A leads to tumors, including those in more than half of colorectal cancers. Instead, Doe and colleagues argue that aurora-A and numb are tumor suppressants under normal conditions, and that a loss of aurora-A is what prompts overproduction of new neuroblasts and, thus, tumor development.
Jim Barlow | EurekAlert!
Molecular microscopy illuminates molecular motor motion
26.07.2017 | Penn State
New virus discovered in migratory bird in Rio Grande do Sul, Brazil
26.07.2017 | Fundação de Amparo à Pesquisa do Estado de São Paulo
Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers
Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...
Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.
At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...
3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects
A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
26.07.2017 | Event News
21.07.2017 | Event News
19.07.2017 | Event News
26.07.2017 | Physics and Astronomy
26.07.2017 | Life Sciences
26.07.2017 | Earth Sciences