A Mayo Clinic Florida researcher and colleagues have discovered a new mechanism to reprogram many types of cancer cells so they're benign and no longer grow.
The discovery by Professor of Cancer Biology Panos Anastasiadis and his co-authors was reported Monday in the prestigious journal Nature Cell Biology.
It has not been tested in human tumors and still requires the development of a therapeutic deliver mechanism.
But the findings introduce a new target for cancer treatments, an early component in the growth of tumors that it is universal to nearly all cancers.
This is noteworthy as cancer is a generalized term for a wide variety of diseases with more than 400 different subtypes.
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"About 90 percent of human cancer starts in epithelial tissues," says Anastasiadis. "These are single-cell layers that line our organs in the lung, breast, colon, and other locations."
In healthy tissues, epithelial cells sit in orderly rows. In cancerous tissues, epithelial cells pile on top of each other in misshapen configurations.
For years researchers have believed that cancer occurs when so-called adhesion proteins that bind cells to their neighbors are unable to tell the cell's internal operating instructions — micro RNA or miRNA for short — that a cell has expanded to meet its neighbor and now must stop growing.
Anastasiadis' team discovered that the outermost adhesion protein — a protein called PLEKHA7 — is effectively the starting mechanism for the internal master switch that tells cells to stop growing.
"If you were to lose that PLEKHA7 or it gets mislocated so the miRNA's were deregulated, the genes driving oncolytic growth were not suppressed, and you get cancer."
Once they knew the properties of PLEKHA7, Anastasiadis team traced its influence to just 27 of the thousands of so-called microRNA molecules that promote gene expression.
"Only a small subset of these microRNA's were regulated by PLEKHA7, but that subset was regulating tumor growth."
"We said, 'what if we restored the miRNA's?' We saw if you do that, you reverse the growth and the cells act as if they were benign."
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Depending upon how the miRNA function has been altered, the team learned, researchers could either increase or reduce their number and as a result, a cancer cell would heed the miRNA instructions and stop growing.
"We get growth inhibition where we were getting uncontrolled growth," says Anastasiadis. "That's why we talk about 're-programming' the cancer cells."
Another unique finding is that the research has connected two previously unrelated areas of cell biology — the study of cell adhesion and that of its genomic instructions.
"Normal cells sense they have proper junctions and stop their growth," he explains.
"This work shows that they do this through the ability to signal the internal growth plan of a cell. The big question," he says, "is can you do it in a tumor in an animal or a human? But it's exciting."
When that time comes, the group plans to target easily accessed cancers, including cancers of the lung and bladder.
The work also holds the potential of a more accurate testing of cancer cells for malignancy.
