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Fruit Flies May Provide Answers to How HPV-induced Cancers Work

AUG 24, 2016 | KRISTI ROSA
A team of researchers from the Zhang lab at the University of Missouri have created the first fruit fly model of human papillomavirus (HPV) induced human cancer. Through the analysis of these fruit flies, scientists hope to better understand the mechanism that allows HPV to cause cancer as well as identify therapies that can potentially treat HPV-induced cancers, according to a press release.

Dr. Bing Zhang, PhD, professor of Biological Sciences and expert on fruit fly (Drosophila melanogaster) genetics at the University of Missouri, and corresponding study author, said, “This is the first in vivo model of an HPV-induced cancer in fruit flies. This new model will allow scientists to exploit a powerful genetic system to understand the molecular and biochemical pathways involved in tumor growth and malignancy caused by HPV as well as screen for potential drug targets.”

The study, led by Dr. Mojgan Padash, PhD, postdoctoral fellow at the University of Missouri and the University of Oklahoma was a collaborative effort; Dr. Vanessa Auld, PhD, professor in the Department of Zoology at the University of British Columbia and Dr. Lawrence Banks, PhD, of the International Centre for Genetic Engineering and Biotechnology in Italy also assisted in the research.

Around 80 million people in the United States alone are infected with HPV, according to the Centers for Disease Control and Prevention (CDC). According to a study analyzing the role of HPV in the development of cervical cancer, “Cervical cancer is one of the leading world causes of cancer morbidity and mortality in women, with more than 98% related to a human papillomavirus (HPV) infection origin.”

In previous studies of mice and human cells, researchers found that the virus uses epithelial skin as a way to enter the body, and once inside, it produces several oncoproteins, which are able to transform normal cells into tumor cells, according to the press release. Viral oncoprotein E6 is found in almost all HPV-postive cancers because it is a contributing factor when it comes to the later stages of tumor formation and metastasis. E6 interacts with normal human proteins, causing them to “lose control.”

The aforementioned human proteins in this interaction are called E6AP, or E6-associated proteins, due to the fact that E6 partners up with E6AP in this process. When combined, they target other human proteins that contain a PDZ domain which then causes them to undergo degradation. Without the normal human proteins, epithelial cells “become disorganized and start uncontrolled proliferation,” according to the press release. A particular protein that tends to be heavily targeted by E6 for degradation is called Magi.

In the new study, viral E6 and human E6AP proteins were introduced to just the wing and the eye epithelial cells in fruit flies. The combined proteins resulted in severe abnormalities within the epithelial cells. In addition, the same suite of PDZ proteins that are targeted by E6 in humans showed reduced levels. The researchers found that the version of the Magi protein found in the fruit flies were still the major target of degradation, just like in human epithelia. “Further experiments done in human cell lines with the fruit fly version of the Magi protein yielded similar results, indicating that the mechanism is highly conserved,” according to the press release.



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