Stress Triggers Cancerous Tumor Formation, Researchers Find

/ Author:  / Reviewed by: Joseph V. Madia, MD

Stress induces signals that cause cells to develop into tumors, Yale researchers have discovered.
The research, published January 13 in Nature, describes a novel way cancer takes hold in the body and suggests new ways to attack the deadly disease.

Until now, most researchers believed more than one cancer-causing mutation needed to take place in a single cell for tumors to grow. The Yale team, led by Tian Xu, professor and vice chair of genetics and a Howard Hughes Medical Institute investigator, illustrated that cancer-causing mutations can cooperate to promote tumor development even when they are located in different cells within a tissue.

"The bad news is that it is much easier for a tissue to accumulate mutations in different cells than in the same cell," said Tian.

The team worked with fruit flies to study the activity of two genes known to be involved in development of human cancers: a gene called RAS that has been implicated in 30 percent of cancers, along with a tumor-suppressing gene called scribble, which contributes to tumor development when mutated. Neither a mutated RAS nor the defective scribble alone can cause cancer. Researchers in Xu's lab previously showed a combination of the two within the same cell could trigger malignant tumors.

However, the Yale team found these mutations did not have to coexist in the same cell to cause tumors. A cell with only mutant RAS can develop into a malignant tumor if helped by a nearby cell with defective scribble. They also found stress conditions such as a wound could trigger cancer formation. For instance, RAS cells developed into tumors when a wound was induced in the tissue. The culprit underlying both phenomena turned out to be a signaling process called JNK, which is activated by environmental stress conditions.

"A lot of different conditions can trigger stress signaling: physical stress, emotional stress, infections, inflammation--all these things. Another bad news for cancer," Xu said.

While the paper shows it is easier than previously thought for cancer to take root in the body, it also identifies new targets to prevent and treat one of the deadliest diseases in the developed world. The team found the JNK stress signaling travels from one cell to the next, but the propagation can be blocked.

"Better understanding of the underlying mechanism causing cancer always offers new tools to battle the disease," Xu said.

The study was funded by the National Cancer Institute and the Howard Hughes Medical Institute.

Contact:
Bill Hathaway
203-432-1322
william.hathaway@yale.edu

Review Date: 
September 17, 2010