Poster abstracts

Poster number 84 submitted by Xin Yin

The roles of ATF3, an adaptive-response gene, in breast cancer development and metastasis

Xin Yin (Ohio State Biochemistry Program, Department of Molecular and Cellular Biochemistry), Tsonwin Hai (Ohio State Biochemistry Program, Department of Molecular and Cellular Biochemistry)

Abstract:
During cancer progression, cells encounter many stress signals and all along they have built-in mechanisms to eliminate themselves. The successful cancer cells manage to foil these hardwired stress responses. Emerging evidence indicates that some of the genes that normally function to eliminate the cells are co-opted to become oncogenes. By gain-of-function and loss-of-function analyses, we found that ATF3, a transcription factor encoded by an adaptive-response gene, exhibits a dichotomous function during cancer progression. ATF3 enhances stress-induced cell death in pre-malignant breast epithelial cells, but protects the highly malignant cancer cells from stress signals. Importantly, ATF3 enhances cell motility in vitro by Boyden chamber assay and enhances metastasis in vivo by orthotopic injection assay. Mechanistic studies revealed that differential gene regulation could be a way by which ATF3 carries out its opposite functions. In addition, ATF3 also functions as a mediator for stromal factors, such as TGF-b, to regulate cancer cell behavior. Preliminary results suggest that ATF3 plays a role in macrophage recruitment and vessel formation, providing a potential mechanism by which ATF3 enhances metastasis.

Keywords: ATF3, Breast cancer, Stromal-cancer interaction