Stress gene implicated in cancer spread
Washington: Researchers have associated the activation of a stress gene in immune-system cells to the spread of breast cancer to other parts of the body.
According to the researchers, 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.
Researchers already know that ATF3 is activated, or expressed, in response to stressful conditions in all types of cells.
Under typical circumstances, turning on ATF3 can actually cause normal and benign 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 coax immune-system cells that have been recruited to the site of a tumor to express ATF3.
Though it`s still unclear how, ATF3 promotes the immune cells to act erratically and give cancer an escape route from a tumor to other areas of the body.
Tsonwin Hai, professor of molecular and cellular biochemistry at The Ohio State University and senior author of the study, said that 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.
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 activate ATF3.
ATF3 is a master switch type of gene: Its gene product, the ATF3 protein, turns on and off other genes. Knowing this, the researchers analyzed the genes that are controlled by ATF3 using a genome-wide global approach. Combining this set of data with another set of data from human samples, Hai and colleagues were able to identify an ATF3 gene signature that can predict whether cancer patients had a low or high risk of dying.
The research has been published in the Journal of Clinical Investigation.