The NFκB subunit RELA is a master transcriptional regulator of the committed epithelial-mesenchymal transition in airway epithelial cells

The Journal of Biological Chemistry
Bing TianAllan R Brasier

Abstract

The epithelial-mesenchymal transition (EMT) is a multistep dedifferentiation program important in tissue repair. Here, we examined the role of the transcriptional regulator NF-κB in EMT of primary human small airway epithelial cells (hSAECs). Surprisingly, transforming growth factor β (TGFβ) activated NF-κB/RELA proto-oncogene, NF-κB subunit (RELA) translocation within 1 day of stimulation, yet induction of its downstream gene regulatory network occurred only after 3 days. A time course of TGFβ-induced EMT transition was analyzed by RNA-Seq in the absence or presence of inducible shRNA-mediated silencing of RELA. In WT cells, TGFβ stimulation significantly affected the expression of 2,441 genes. Gene set enrichment analysis identified WNT, cadherin, and NF-κB signaling as the most prominent TGFβ-inducible pathways. By comparison, RELA controlled expression of 3,138 overlapping genes mapping to WNT, cadherin, and chemokine signaling pathways. Conducting upstream regulator analysis, we found that RELA controls six clusters of upstream transcription factors, many of which overlapped with a transcription factor topology map of EMT developed earlier. RELA triggered expression of three key EMT pathways: 1) the WNT/β-catenin morphogen...Continue Reading

References

Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·A A Postigo, D C Dean
Jan 22, 2002·The Journal of Biological Chemistry·Andreas BirbachJohannes A Schmid
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Aug 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yaw-Ching YangErwin P Böttinger
Oct 9, 2003·The EMBO Journal·Alexander HoffmannDavid Baltimore
Jan 8, 2004·Respirology : Official Journal of the Asian Pacific Society of Respirology·Darryl A Knight, Stephen T Holgate
Mar 31, 2005·Biochemical and Biophysical Research Communications·Akio KanazawaShiro Maeda
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
May 11, 2006·Differentiation; Research in Biological Diversity·Melville B VaughanJerry W Shay
Aug 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Kevin K KimHarold A Chapman
Feb 17, 2007·Cardiovascular Toxicology·Allan R Brasier
Dec 24, 2008·Molecular and Cellular Biology·Bo HuangLin-Feng Chen
Mar 13, 2009·Organogenesis·Yuko Komiya, Raymond Habas
May 9, 2009·International Journal of Molecular Medicine·Masuko Katoh, Masaru Katoh
Jun 3, 2009·The Journal of Clinical Investigation·Raghu Kalluri, Robert A Weinberg
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Zhan YaoRaffaella Sordella
Sep 21, 2010·The Journal of Clinical Investigation·Kristina E HootXiao-Jing Wang
Nov 25, 2011·Methods in Molecular Biology·Bing TianAllan R Brasier
May 9, 2012·Nature Medicine·Bart N Lambrecht, Hamida Hammad
May 17, 2012·Science Signaling·Ju BaoDianqing Wu
Jun 12, 2012·Cell·Hans Clevers, Roel Nusse
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Dec 1, 2012·Current Opinion in Oncology·Yoko KatsunoRik Derynck
Apr 26, 2013·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Maki KanzawaHiroshi Yokozaki
Sep 6, 2013·Epigenetics & Chromatin·Marcin CieślikStefan Bekiranov
Oct 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Mingyang LuEshel Ben-Jacob
Nov 15, 2013·BioMed Research International·Mridul KalitaAllan R Brasier

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Citations

Sep 23, 2018·Expert Review of Respiratory Medicine·Allan R Brasier
Feb 5, 2019·Expert Review of Respiratory Medicine·Allan R Brasier
Nov 30, 2019·Frontiers in Pharmacology·Jose Luis Morgado-PascualMarta Ruiz-Ortega
Nov 27, 2019·Cells·Dmitri TentlerNikolai A Barlev
Jul 11, 2020·Signal Transduction and Targeted Therapy·Bing ZhaoWei Mo
Apr 3, 2020·Molecular Biology Reports·George I LambrouSpiros Vlahopoulos
Mar 11, 2020·International Journal of Molecular Sciences·Brooke ArmisteadHamid-Reza Kohan-Ghadr
Oct 25, 2020·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Adam HermawanRohmad Yudi Utomo
Jul 4, 2020·Cancer Research·Foteinos-Ioannis D DimitrakopoulosHaralabos P Kalofonos
Oct 1, 2018·Pharmacology & Therapeutics·Mohit Kumar JollyHerbert Levine
Apr 2, 2021·Investigative Ophthalmology & Visual Science·Srinivasa R SripathiDonald J Zack
May 22, 2021·Expert Review of Proteomics·Morgan Mann, Allan R Brasier
Jul 29, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Dianhua QiaoAllan R Brasier

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