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January 13, 2010

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Stress may cause cancer, study suggests

Jan. 13, 2010
Courtesy Yale University
and World Science staff

Stress may cause cells to be­come can­cer­ous, Yale Uni­vers­ity sci­en­tists have found, in a study that al­so sug­gests new ways to at­tack the deadly dis­ease.

Un­til now, most re­search­ers thought more than one can­cer-caus­ing muta­t­ion had to oc­cur in the same cell to make tu­mors grow. But the Yale team, led by ge­net­i­cist Tian Xu, found this can oc­cur even if the muta­t­ions arise in dif­fer­ent, near­by cells.

“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, whose re­search was pub­lished on­line Jan. 13 in the jour­nal Na­ture.

His team worked with fruit flies to study the ac­ti­vity of two genes in­volved in can­cer: a gene called RAS that has been im­pli­cat­ed in 30 per­cent of can­cers, and a tu­mor-suppressing gene called scrib­ble, which con­tri­butes to tu­mor de­vel­op­ment when mu­tat­ed. Nei­ther de­fec­tive gene alone can cause can­cer. 

Re­search­ers in the Xu lab pre­vi­ously showed that a com­bina­t­ion of the two with­in the same cell could trig­ger ma­lig­nant tu­mors.

The Yale team has now found these muta­t­ions need not co-exist in one 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. The group 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 chem­i­cal sig­nal­ing pro­cess called JNK, which is ac­tivated by en­vi­ron­men­tal stress con­di­tions, Xu ex­plained.

“A lot of dif­fer­ent con­di­tions can trig­ger stress sig­nal­ing: phys­i­cal stress, emo­tion­al stress, in­fec­tions, in­flamma­t­ion,” Xu said. It’s more “bad news for can­cer,” he added.

But the good news is that the re­search al­so iden­ti­fies new tar­gets to pre­vent and treat one of the dead­li­est dis­eases in the de­vel­oped world, Xu said. The Yale team found that the JNK stress sig­nal­ing trav­els from one cell to the next, but that the propaga­t­ion can be blocked.

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

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Stress may cause cells to become cancerous, Yale University scientists have found, in a study that also suggests new ways to attack the deadly disease. Until now, most researchers thought more than one cancer-causing mutation needed to occur in the same cell in order for tumors to grow. But the Yale team, led by geneticist Tian Xu, found this can occur even if the mutations occur in different, nearby cells. “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, whose research was published online Jan. 13 in the journal Nature. His team worked with fruit flies to study the activity of two genes involved in cancer: a gene called RAS that has been implicated in 30 percent of cancers, and a tumor-suppressing gene called scribble, which contributes to tumor development when mutated. Neither defective gene alone can cause cancer. Researchers in the Xu lab previously showed that a combination of the two within the same cell could trigger malignant tumors. The Yale team has now found that these mutations didn’t have to co-exist in one 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. The group 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 chemical signaling process called JNK, which is activated by environmental stress conditions, Xu explained. “A lot of different conditions can trigger stress signaling: physical stress, emotional stress, infections, inflammation – all these things,” Xu said, more “bad news for cancer.” The good news is that the research also identifies new targets to prevent and treat one of the deadliest diseases in the developed world, Xu said. The Yale team found that the JNK stress signaling travels from one cell to the next, but that the propagation can be blocked. “Better understanding of the underlying mechanism causing cancer always offers new tools to battle the disease,” Xu said.