Learning about human cancer from fruit flies

Scientists in Singapore and Spain have gained new insights into the activity of a tumor-suppressing protein in fruit flies, which may help understand some cancers in humans. The study, published in PLOS Biologycould eventually lead researchers to new cancer treatments and prevention.

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

While fruit flies and humans may appear very different, researchers often find that crucial molecular pathways, signaling and control systems are shared by many species, having evolved early in evolution from a diverse variety of organisms.

“Because Hyrax – an evolutionarily related protein – is the analog of Parafibromin, we investigated it in brain cell development in Drosophila fruit flies as a first step towards a better understanding,” said Dr. Deng Qiannan, lead author of the study and Research Fellow. with the Neuroscience and Behavioral Disorders (NBD) program at Duke-NUS.

“We found that the Hyrax protein plays an essential role during the development of the Drosophila central nervous system, so we think parafibromin may also perform a similar function in humans,” says Dr. Cayetano Gonzalez, a co-author of the study. and head of the Cell Division Laboratory at the Institute for Research in Biomedicine, Barcelona.

The results revealed previously undiscovered functions for the protein in controlling cell polarity – the asymmetric organization of proteins – in the stem cells that generate mature nerve cells. Loss of Hyrax function was found to lead to the overgrowth of neural stem cells in the Drosophila brain. This was linked to influences on cell structures called centrosomes, which coordinate cell division, and to 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, the study’s corresponding senior author and deputy director of the NBD Program at Duke-NUS. “These surprising new findings may be very relevant to understanding parafibromin’s role in human cancers, perhaps especially in the brain.”

More research will be needed to investigate whether these fruit fly findings can be applied to Parafibromin in humans and the research team has already started new studies towards this goal.

“Translating basic scientific research into discoveries of clinical significance is a primary goal of medical research. Professor Wang and her colleagues have taken a very interesting first step that could one day have an impact on cancer treatment and prevention,” says Professor Patrick Casey, Senior Vice Dean of Research at Duke-NUS.