Chris Flynn/UCLA Dentistry
Dr. Paul Krebsbach
Once they identified mEAK-7 in human cells, they screened several types of human cells — including embryonic stem cells and fibroblasts, the cells that form connective tissues and aid in wound healing — to better understand how the gene worked.
“We didn’t detect mEAK-7 in any of those samples,” said Nguyen, a D.D.S./Ph.D. candidate at the University of Michigan. “But what we did find was astonishing. When we tested for mEAK-7 in various cancer cells, we found that there was a notably high concentration of mEAK-7 protein.”
The researchers ran a series of tests on human cells to see how mEAK-7 responded to a biological process known as mTOR signaling, which regulates cell metabolism, growth, duplication and survival in humans.
According to Krebsbach, what they found was even more astonishing than the uncovering of mEAK-7 itself. The gene actually activated another biological process, which the researchers call an alternative pathway, one that was not as well understood at the molecular level as mTOR.
In effect, the discovery was like realizing that a driver (the mEAK-7 gene) had exited a freeway (the mTOR pathway) and chosen to travel little-known surface streets (the alternative pathway) to reach his destination.
“With the discovery of mEAK-7’s activation of this alternative process, we demonstrated that cell metabolism, division and migration may be more dependent on the type of cell than was previously understood,” Krebsbach said. “If we can find a way to control the duplication and migration of cells, including those responsible for human disease, we may be able to create opportunities for new therapies.”
To support their findings, the scientists tested the significance of mEAK-7’s role in cell proliferation and migration by inhibiting the gene in living human cells. When they mutated mEAK-7 or removed it from those cells, there was a dramatic reduction of those processes. They also tested a scenario in which mEAK-7 was overexpressed in cells and found that the proliferation of those cells increased significantly.
“By chance, we have found that mEAK-7 is crucial for mTOR signaling and is required for cell proliferation and migration,” said Jin Koo Kim, a UCLA Dentistry researcher. “By targeting mEAK-7, we could potentially control the diseases that hijack mTOR signaling through this alternative pathway.”
The study was made possible in part by the National Institute of Dental and Craniofacial Research and the Stuart and Barbara Padnos Research Award from the Comprehensive Cancer Center at the University of Michigan. The authors have no competing interests.
