title: MTA1 promotes STAT3 transcription and pulmonary metastasis in breast cancer.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia 20037, USA.
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Pakala
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Rayala
authors.forename: Rui-An
authors.initials: RA
authors.lastname: Wang
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Ohshiro
authors.forename: Prakriti
authors.initials: P
authors.lastname: Mudvari
authors.forename: Sirigiri Divijendra Natha
authors.initials: SD
authors.lastname: Reddy
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pires
authors.forename: Sandra
authors.initials: S
authors.lastname: Casimiro
authors.forename: M Radhakrishna
authors.initials: MR
authors.lastname: Pillai
authors.forename: Luis
authors.initials: L
authors.lastname: Costa
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D004257:DNA Polymerase II / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C503336:Mta1 protein, mouse; D009687:Nuclear Proteins; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse; D004257:DNA Polymerase II