Researchers Identify Point In Cell Development Where A 'Wrong Turn' Can Lead To Cancer

U.S. researchers say they've pinpointed the point at which cell development can go awry and a cell can take a "wrong turn" to become cancerous.

Scientists at Northwestern University say they used cells in a fruit fly's eye to find how normal cells can experience bad developmental changes during their life cycle and become cancer cells.

They studied a fruit fly oncogene (a gene that can sometimes switch a cell into a tumor cell) similar to a human equivalent linked with many types of leukemia in an effort to understand how developing cells will normally switch from a stem-cell-like undifferentiated state to a more specialized state, and the way cancer might result if that process goes wrong.

Looking at how cells normally behave in the developing eye, the scientists discovered levels of a vital protein identified as Yan fluctuated wildly as the cell prepared to change from a primitive, stem-like configuration to a more specialized one.

If those protein levels don't fluctuate, or can't, the cell will not switch and cannot forward, they found.

"This mad fluctuation, or noise, happens at the time of cell transition," says Richard W. Carthew, a professor of molecular biosciences in Northwestern's Weinberg College of Arts and Sciences.

In that brief interval as the developing cell changes from state A to state B, he explains, the noise represents an important state of "in between" vital for the cell's ability to switch to a more specialized state.

"This limbo might be where normal cells take a cancerous path," he suggests.

The noise is only turned off when a cell receptor known as EGFR receives the proper molecular signal, and if that signal is not received, the cell will remain in an uncontrolled state, the researchers say.

In a fruit fly it takes 15 to 20 hours for a cell to change from unrestricted to specialized, and the Yan protein is fluctuating, or "noisy," for 6 to 8 hours, the researchers found.

The discovery that this cellular noise and its controlling "off" switch are important factors in the process of normal cell differentiation provides new avenues for studying how cell development can get out of control and cells can turn cancerous, the researchers say in their study published in the biomedical journal eLife.

In humans, a protein knows as Tel-1, similar to the fruit fly's Yan protein, causes cells to develop into white blood cells.

The gene responsible for producing that protein, oncogene Tel-1, frequently mutates incorrectly into leukemia, the researchers point out.

"On the surface, flies and humans are very different, but we share a remarkable amount of infrastructure," Carthew says. "We can use fruit fly genetics to understand how humans work and how things go wrong in cancer and other diseases."

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