Tumor and Stem Cell Biology MTA1 Promotes STAT3 Transcription and Pulmonary Metastasis in Breast Cancer

Overexpression of the prometastatic chromatinmodifier proteinmetastasis tumor antigen 1 (MTA1) in human cancer contributes to tumor aggressiveness, but the role of endogenous MTA1 in cancer has not been explored. Here, we report the effects of selective genetic depletion ofMTA1 in a physiologically relevant spontaneousmouse model of breast cancer pulmonary metastasis. We found that MTA1 acts as a mandatory modifier of breast-tolung metastasis without effects on primary tumor formation. The underlying mechanism involved MTA1dependent stimulation of STAT3 transcription through action on the MTA1/STAT3/Pol II coactivator complex, and, in turn, on the expression and functions of STAT3 target genes including Twist1. Accordingly, we documented a positive correlation between levels of MTA1 and STAT3 in publicly available breast cancer data sets. Together, our findings reveal an essential modifying role of the physiologic level of MTA1 in supporting pulmonary metastasis of breast cancer. Cancer Res; 73(12); 1–10. 2013 AACR.