Research Projects

Transforming growth factor-beta1 (TGF-beta1) is a crucial cytokine in maintaining cell homeostasis and suppressing tumor progression. However, breast cancer progresses when this anti-proliferative response is lost. TGF-beta1's disturbance in cancer is attributed to a small group of immediate TGF-beta1 target genes. TGF-beta1 strongly stimulates and maintains the level of activating transcription factor-3 (ATF-3) in human breast cancer cells and mouse mammary pad tumor cells. ATF-3 is also highly expressed in human primary tumor tumors, with Cyclin A1, MMP-13, and Runx2 being ATF-3 target genes. This proposal aims to identify and functionally characterize TGF-beta1-stimulated ATF-3 sumoylation and its sites using in vitro and in vivo models. The findings could lead to translational research for developing small molecules against ATF-3 sumoylation in controlling breast cancer progression and bone metastasis.