MTA1 Promotes STAT3 Transcription and Pulmonary Metastasis in Breast Cancer

作者：Pakala Suresh B; Rayala Suresh K; Wang Rui An; Ohshiro Kazufumi; Mudvari Prakriti; Reddy Sirigiri Divijendra Natha; Zheng Yi; Pires Ricardo; Casimiro Sandra; Pillai M Radhakrishna; Costa Luis; Kumar Rakesh^*

来源：Cancer Research, 2013, 73(12): 3761-3770.

DOI：10.1158/0008-5472.CAN-12-3998

Overexpression of the prometastatic chromatin modifier protein metastasis 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 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.

• 出版日期2013-6-15
• 单位河北医科大学