MTA1 Promotes STAT3 Transcription and Pulmonary Metastasis in Breast Cancer

Biochemistry and Molecular Biology, The George Washington University Medical Center.
Cancer Research (Impact Factor: 9.33). 04/2013; 73(12). DOI: 10.1158/0008-5472.CAN-12-3998
Source: PubMed


Overexpression of the pro-metastatic chromatin modifier protein 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 of MTA1 in a physiologically relevant spontaneous mouse model of breast cancer pulmonary metastasis. We found that MTA1 acts as a mandatory modifier of breast-to-lung metastasis without effects on primary tumor formation. The underlying mechanism involved MTA1-dependent 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.

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