To our knowledge, this is the first report demonstrating the ability of ATF3 to enhance breast cancer-initiating cell features and to feedback on TGFβ.
This transgenic mouse model system reproduces some features of human breast cancer in that about 20% of human breast tumor specimens exhibit overexpression of ATF3 in the tumor cells.
In conclusion, we identified ATF3 as a regulator in myeloid cells that enhances breast cancer metastasis and has predictive value for clinical outcomes.
Transforming growth factor-beta1 (TGF-β1) plays a significant role in breast cancer mediated bone metastasis, and it stimulated expression of matrix metalloproteinase-13 (MMP-13; an invasive and metastasis gene) via activating transcription factor-3 (ATF-3) in human breast cancer cells (MDA-MB231).
However, its upregulator remains largely unknown. miRNA modulate gene expression by post-transcriptional repression to participate in many signaling pathway of breast cancer cell proliferation. miR-590 has been reported to regulate tumorgenesis and could be regulated by its own target ATF-3.
In this review, the structure and function of ATF3, its posttranslational modifications (PTM), and its interacting proteins are discussed with a special emphasis on breast cancer metastasis.