Stress Gene Facilitates Breast Cancer Metastasis
In an unexpected finding, scientists have linked the activation of a stress gene in immune-system cells to breast cancer metastasis and patient outcome.
Senior author and OSUCCC – James researcher Tsonwin Hai, PhD, professor of Molecular and Cellular Biochemistry, says the study suggests that the gene, called ATF3, may be a crucial link between stress, cancer and a tumor cell’s ability to metastasize.
The results provide important insights into how tumor cells co-opt immune cells to enhance breast cancer metastasis, and they suggest that the stress gene could be a valuable drug target for inhibiting metastasis, Hai says. Additional research must confirm these results. Previous public health studies have shown that stress is a risk factor for cancer, and researchers already knew that ATF3 is activated, or expressed, when cells are stressed. Under typical circumstances, ATF3 activation can cause normal and benign cells to self-destruct if stressors such as irradiation or a lack of oxygen irrevocably damage the cells.
This research suggests that cancer cells coax immune cells present in the tumor to express ATF3. This then somehow causes the immune cells to act erratically, enabling tumor cells to escape to other areas of the body.
Hai and her colleagues first linked ATF3 expression in tumor-associated immune cells to worse outcomes among a sample of almost 300 breast-cancer patients. They followed that with animal studies and found that mice lacking ATF3 had fewer metastatic tumors to the lungs than did normal mice that expressed the gene.
Published in the Journal of Clinical Investigation.
NIH/National Cancer Institute grants CA118306, CA090223; NIH/National Institute of Environmental Health Sciences grant ES021018; National Institutes of Health grant NS045758; research programs in Australia; and a Pelotonia Idea Grant supported this research.