MTA1 Promotes STAT3 Transcription and Pulmonary Metastasis in Breast Cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 12; pp. 3761 - 3770
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.06.2013
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Blotting, Western; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Movement - genetics; Cells, Cultured; DNA Polymerase II - metabolism; Female; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Mammary gland diseases; Mammary Neoplasms, Animal - genetics; Mammary Neoplasms, Animal - metabolism; Mammary Neoplasms, Animal - pathology; Medical sciences; Mice; Mice, 129 Strain; Mice, Knockout; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pharmacology. Drug treatments; Pneumology; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Tumors; Tumors of the respiratory system and mediastinum; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism; Mammary gland diseases; Lung disease; Metastasis associated gene 1; Breast disease; Lung metastasis; Transcription; Respiratory disease; Breast metastasis; Transcription factor STAT3; Breast cancer; Malignant tumor; Cancer
• ISSN: 0008-5472; 1538-7445; 1538-7445
• 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. Cancer Res; 73(12); 3761–70. ©2013 AACR.