Stress has long been known to promote cancer and other health conditions. Now, scientists say they know why. New research out of Ohio State University has identified a molecular "master switch" activated by a stress-related gene that causes the spread of breast cancer to other parts of the body.
Researchers say the study suggests the gene, called ATF3, is the key link between stress and cancer, including the major cause of cancer death — its spread (metastasis). Past studies have shown ATF3 is activated in response to stressful conditions in all types of cells. ATF3 can cause normal healthy cells to die if stressors, such as irradiation and a lack of oxygen, have damaged them.
"It's like what Pogo said: 'We have met the enemy, and he is us,' " said lead researcher Tsonwin Hai, professor of molecular and cellular biochemistry at Ohio State University. "If your body does not help cancer cells, they cannot spread as far. So really, the rest of the cells in the body help cancer cells to move, to set up shop at distant sites. And one of the unifying themes here is stress."
For the new research, Hai and colleagues linked the activation of the ATF3 gene to worse outcomes among nearly 300 breast-cancer patients. They then conducted animal studies and found that mice lacking the ATF3 gene had less extensive metastasis of breast cancer to their lungs than did normal mice that could activate ATF3.
Hai said the stress gene may one day be targeted by drugs to combat the spread of cancer metastasis. In the meantime, she said the results provide important insights into how tumors coopt the rest of the body into aiding cancer's survival and movement to distant organs.
Hai explained that when cancer cells first appear, the immune system recognizes them as foreign and attacks them. But as cancer cells grow, they send out certain molecular messengers to promote a chronic wound-healing response from the immune system. Tumor cells then hijack that process to thrive and spread.
"If the body is in perfect balance, there isn’t much of a problem," Hai noted. "When the body gets stressed, that changes the immune system. And the immune system is a double-edged sword.
"ATF3 induction in immune cells is one way this probably happens. We’re not saying it's the only way."
The study was funded, in part, by the National Institutes of Health.
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