Loss of BRMS1 promotes a mesenchymal phenotype through NF-κB-Dependent regulation of twist1 Journal Article

   


Authors: Liu, Y.; Mayo, M. W.; Xiao, A.; Hall, E. H.; Amin, E. B.; Kadota, K.; Adusumilli, P. S.; Jones, D. R.
Article Title: Loss of BRMS1 promotes a mesenchymal phenotype through NF-κB-Dependent regulation of twist1
Abstract: Breast cancer metastasis suppressor 1 (BRMS1) is downregulated in non-small cell lung cancer (NSCLC), and its reduction correlates with disease progression. Herein, we investigate the mechanisms through which loss of the BRMS1 gene contributes to epithelial-to-mesenchymal transition (EMT). Using a short hairpin RNA (shRNA) system, we show that loss of BRMS1 promotes basal and transforming growth factor beta-induced EMT in NSCLC cells. NSCLC cells expressing BRMS1 shRNAs (BRMS1 knockdown [BRMS1KD]) display mesenchymal characteristics, including enhanced cell migration and differential regulation of the EMT markers. Mesenchymal phenotypes observed in BRMS1KD cells are dependent on RelA/p65, the transcriptionally active subunit of nuclear factor kappa B (NF-κB). In addition, chromatin immunoprecipitation analysis demonstrates that loss of BRMS1 increases Twist1 promoter occupancy of RelA/p65 K310-a key histone modification associated with increased transcription. Knockdown of Twist1 results in reversal of BRMS1KD-mediated EMT phenotypic changes. Moreover, in our animal model, BRMS1KD/Twist1KD double knockdown cells were less efficient in establishing lung tumors than BRMS1KD cells. Collectively, this study demonstrates that loss of BRMS1 promotes malignant phenotypes that are dependent on NF-κB-dependent regulation of Twist1. These observations offer fresh insight into the mechanisms through which BRMS1 regulates the development of metastases in NSCLC.
Keywords: controlled study; protein phosphorylation; unclassified drug; human cell; disease course; nonhuman; comparative study; phenotype; cell viability; mesenchyme cell; reverse transcription polymerase chain reaction; gene expression; transforming growth factor beta; immunoglobulin enhancer binding protein; cell differentiation; transcription factor rela; immunofluorescence; uvomorulin; animalia; regulatory mechanism; microarray analysis; chromatin immunoprecipitation; western blotting; reporter gene; cell migration; epithelium cell; down regulation; tumor suppressor protein; transcription factor twist; cell invasion; short hairpin rna; vimentin; plasmid dna; non small cell lung cancer; colony formation; synaptotagmin i; epithelial mesenchymal transition; histone modification; rna isolation; gene ontology; human; article; breast cancer metastasis suppressor 1; transcription factor twist1
Journal Title: Molecular and Cellular Biology
Volume: 35
Issue: 1
ISSN: 0270-7306
Publisher: American Society for Microbiology  
Date Published: 2015-01-01
Start Page: 303
End Page: 317
Language: English
DOI: 10.1128/mcb.00869-14
PROVIDER: scopus
PMCID: PMC4295387
PUBMED: 25368381
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84920019805&partnerID=40&md5=1159c83e1e8073ef9e3312c9cf772330
Notes: Export Date: 2 February 2015 -- Source: Scopus
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MSK Authors
  1. Kyuichi Kadota
    85 Kadota
  2. Prasad S Adusumilli
    496 Adusumilli
  3. Elianna Binte Mohamed Amin
    10 Mohamed Amin
  4. David Randolph Jones
    417 Jones
  5. Yuan Liu
    22 Liu
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