Scientists at John Hopkins Institute for Basic Biomedical Scientists have identified a protein in fruit flies that controls organ size and, when overabundant, causes the same aberrational cell behavior (increased growth and decreased death) associated with cancer.
The “Yorkie” protein, as it became referred to, is significant in that it has a counterpart in mammals called YAP which appears to have the same effect on cell behavior and thus may play some role in the development of cancer.
The findings are based largely on the work of Duojia Pan, Ph.D., who carried out the majority of the research at the University Of Texas Southwestern Medical Center at Dallas before coming to the Johns Hopkins.
Other authors of the study, which was funded by the National Institutes of Health and is published in the August 12 issue of Cell, included Shian Wu from Hopkins, and Jianbin Huang, Jose Barrera and Krista Matthews from University of Texas Southwestern.
Pan’s earlier studies determined that fruit flies missing a gene called hippo developed tumors. His research then documented a chain reaction of proteins made by hippo and similar genes with other unidentified proteins.
That chain reaction functions to chemically add phosphates to the other unknown proteins. This process, called phosphorylation, appears to help control the growth of cells.
"From those results, we predicted that another protein must be involved in the tumor-suppression pathway that is a target of the phosphorylation cascade," said Pan.
That “other” protein has now been identified as Yorkie. Pan and his colleagues documented that the hippo phosphorylation cascade turns Yorkie off. When Yorkie levels were too high, more tissue cells grew and fewer died, a condition that is a “hallmark” of cancer.
Additional experiments in the fruit fly replaced Yorkie with YAP and confirmed that the two proteins function in similar ways. Therefore, YAP may participate in a tumor-related pathway in mammals.
Currently, Pan is trying to determine the signal that tells genes like hippo to turn on or off once an organ grows to the appropriate size. Results of this research could be used in future cancer therapies.