In an unexpected finding, scientists have linked the activation¹ of a stress gene² in immune-system cells to the spread of breast cancer to other parts of the body. Researchers say the study suggests this gene, called ATF3, may be the crucial link between stress and cancer, including the major cause of cancer death -- its spread, or metastasis（转移，新陈代谢）. Previous public health studies have shown that stress is a risk factor for cancer.

 

Researchers already know that ATF3 is activated⁴, or expressed, in response to stressful conditions in all types of cells. Under typical circumstances, turning on ATF3 can actually cause normal and benign⁵ cells to commit suicide if the cells decide that the stressors, such as irradiation and a lack of oxygen, have irrevocably damaged the cells.

 

This research suggests, however, that cancer cells somehow coax⁶ immune-system cells that have been recruited to the site of a tumor⁷ to express ATF3. Though it's still unclear how, ATF3 promotes the immune cells to act erratically⁸ and give cancer an escape route from a tumor to other areas of the body.

 

"It's like what Pogo said: 'We have met the enemy, and he is us,'" said Tsonwin Hai, professor of molecular⁹ and cellular¹⁰ biochemistry at The Ohio State University and senior author of the study. "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 unifying¹¹ themes here is stress."

 

Hai and colleagues first linked the expression of the ATF3 gene in immune-system cells to worse outcomes among a sample of almost 300 breast-cancer patients. They followed with 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 activate³ ATF3.

 

This stress gene could one day function as a drug target to combat cancer metastasis if additional studies bear out these results, Hai said. In the meantime, she said the results provide important insights into how cells in a tumor use their signaling power to coopt the rest of the body into aiding cancer's survival and movement to distant organs.

 

The research is published in a recent issue of the Journal of Clinical Investigation¹².

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