When speaking of the implications of the findings, Dr. Padash said, “This finding prompted us to see if expression of Magi could suppress the E6-medicated cellular abnormalities in fruit fly, which it did, again reinforcing that Magi is an important player.”
The scientists found that the co-expression of viral E6 and human E6AP were insufficient in causing tumors within flies, despite the noted cellular abnormalities. These findings were consistent with the findings of HPV E6-induced cancer found in humans, according to the study authors.
Presented with these findings, Dr. Padash hypothesized, “In humans, there is a period of 15-20 years from the time of HPV infection to the development of cancer, suggesting that cooperation between E6 and E6AP is not sufficient to induce cancer. It is thought that mutations in another oncoprotein, called Ras, may contribute to the E6-mediated tumorigenesis in humans.”
The scientists then proceeded to express the viral E6 and human E6AP in the presence of a mutated version of the oncoprotein, Ras, in the fruit flies in order to test their hypothesis. The combination of all three proteins resulted in the development of malignant tumors in the fruit flies that “metastasized from the eyes to the rest of the body,” according to the press release.
Dr. Padash said, “The take home message is that the same key molecular players that underlie HPV E6-mediated cancer in humans do the same things in flies, which suggests that the mechanism is highly conserved. Practically speaking, this means we can now use this fly model to identify other essential components or elements that contribute to E6-mediated tumorigenesis.”
The researchers demonstrated the potential of these findings when they identified an insulin receptor that interacts through E6, found when they conducted an initial genetic screen. After identifying the insulin receptor, they then introduced it to fruit flies that had both viral E6 and human E6AP proteins, which resulted in cell proliferation. The suggests “that insulin may play a role in cancer progression induced by HPV,” according to the press release.
When speaking of how the meaning of these results, Dr. Banks, commented, “From a basic science point of view, it shows that the mechanisms by which the HPV E6 oncoprotein targets essential cellular regulatory pathways are conserved across evolution, suggesting that these targets, as exemplified by Magi, are of fundamental importance in controlling cell growth and proliferation.” He then added, “From a more practical point of view, the power of this model is that it can be used now to screen for inhibitors of other pathways, which have the potential to translate into therapies for HPV-induced cancers.”
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