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Learn more about human fruit fly cancer

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Loss of Parafibromin/Hyrax results in loss of neural stem cell (NSC) polarity, leading to a shift from asymmetric to symmetric division. Upper panels: Dividing NSCs from control (left) and Hyrax knockdown (right) were labeled with cell-polarity protein aPKC (gray) and DNA (cyan). The asymmetric localization of aPKC is lost in the knockdown. Lower panels: Brain telophase NSCs were labeled with a phospho-Histone H3 mitotic marker (PH3 in magenta) and a GFP membrane marker (green) marking the cell outline. Blue lines and red lines indicate the diameter of two NSC daughter cells. Control NSC (left) divides asymmetrically to produce two daughter cells of distinct sizes, while Hyrax knockdown NSC (right) divides symmetrically to generate two daughter cells of similar sizes. Scale bars: 5 mm. 1 credit: Duke-NUS

Scientists from Singapore and Spain have gained new insights into the activity of a tumor suppressor protein in fruit flies that could help understand certain human cancers. The study, published in PLOS Biologycould eventually lead researchers to new cancer treatments and prevention.

Scientists at Duke-NUS Medical School collaborated with colleagues from the Institute for Biomedicine Research at the Institute of Science and Technology in Barcelona, ​​the Genome Institute in Singapore and NUS to study a human tumor suppressor protein called parafibromin. Parafibromin’s normal activities prevent tumors from growing, but deficiencies in these activities have been linked to several cancers, including hyperparathyroidism-jaw tumor syndrome and breast, gastric, colorectal, and lung cancers. Until now, the protein’s exact role in nervous system health and disease has remained unknown.

Although fruit flies and humans may look very different, researchers often find that crucial molecular pathways, signaling and control systems are shared by many species, having originated early in the evolution of a wide variety of organisms.

“As Hyrax – an evolutionary-related protein – is the analogue of parafibromin, we examined it in the development of brain cells in Drosophila fruit flies as a first step towards a better understanding,” said Dr. Deng Qiannan, first author of the study and researcher. with the Neurosciences and Behavioral Disorders (NBD) program at Duke-NUS.

“We found that the Hyrax protein plays a critical role during Drosophila central nervous system development, and therefore we believe that parafibromin may also perform a similar function in humans,” said Dr. Cayetano Gonzalez, co – author of the study. and Head of the Cell Division Laboratory at the Barcelona Biomedicine Research Institute.

The results revealed previously unknown functions of the protein in controlling cell polarity – the asymmetric organization of proteins – in stem cells that generate mature nerve cells. Loss of Hyrax function has been found to lead to the proliferation of neural stem cells in the Drosophila brain. This was linked to influences on cellular structures called centrosomes, which coordinate cell division, and the regulation of two other known tumor suppressor proteins, Polo and Aurora-A kinases.

“Loss of cell polarity and centrosomal abnormalities are hallmarks of human cancers,” said Professor Wang Hongyan, corresponding senior author of the study and deputy director of the NBD program at Duke-NUS. “These surprising new findings may be very relevant to understanding the role of parafibromin in human cancers, perhaps especially in the brain.”

Further research will be needed to determine if these findings in fruit flies can be applied to parafibromin in humans, and the research team has already begun new investigations with this aim.

“Translating basic scientific research into discoveries of clinical significance is one of the primary goals of medical research. Professor Wang and his colleagues have taken a very exciting first step that could one day have an impact on cancer treatment and prevention,” said Professor Patrick Casey, Associate Dean Director for Research at Duke-NUS.


Proteins resist nerve cell regression


More information:
Qiannan Deng et al, parafibromin governs cell polarity and centrosome assembly in Drosophila neural stem cells, PLOS Biology (2022). DOI: 10.1371/journal.pbio.3001834

Provided by Duke-NUS Medical School


Quote: Read more about human cancer in fruit flies (October 19, 2022) retrieved October 20, 2022 from https://phys.org/news/2022-10-human-cancer-fruit-flies.html

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