(HealthDay News) – Activating transcription factor 3 (ATF3), at the center of the cellular adaptive response network, plays a key role in host cell enhancement of breast cancer metastasis, according to a study published in the July 1 issue of the Journal of Clinical Investigation.
Chris C. Wolford, from The Ohio State University in Columbus, and colleagues investigated the molecular mechanisms underlying host response to cancer signals in the development of breast cancer.
The researchers found that ATF3 plays an important role in enhancing breast cancer metastasis in host cells. In patient tumor samples, ATF3 expression in stromal mononuclear cells, but not cancer epithelial cells, correlated with worse clinical outcomes and independently predicted breast cancer death. In mouse models, breast cancer metastasis was less efficient in Aft3-deficient vs. wild-type mice. Fewer lung metastases were seen in mice with myeloid cell-selective knock out of Atf3. An ATF3-regulated gene signature was identified that could differentiate human tumor stroma from distant stroma, and could predict clinical outcomes in gene profiling analyses of macrophages from mouse tumors.
“In conclusion, we identified ATF3 as a regulator in myeloid cells that enhances breast cancer metastasis and has predictive value for clinical outcomes,” the authors write.