title: JunB contributes to Id2 repression and the epithelial-mesenchymal transition in response to transforming growth factor-β.
abstract: The process of epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β) contributes to tissue fibrosis, wound healing, and cancer via a mechanism that is not fully understood. This study identifies a critical role of JunB in the EMT and profibrotic responses to TGF-β. Depletion of JunB by small interfering ribonucleic acid abrogates TGF-β-induced disruption of cell-cell junctions, formation of actin fibers, focal adhesions, and expression of fibrotic proteins. JunB contributes to Smad-mediated repression of inhibitor of differentiation 2 through interaction with transcription repressor activating transcription factor 3. Importantly, JunB mediates the TGF-β induction of profibrotic response factors, fibronectin, fibulin-2, tropomyosin (Tpm1), and integrin-β3, which play critical roles in matrix deposition, cell-matrix adhesion, and actin stress fibers. In summary, JunB provides important input in setting the transcriptional program of the EMT and profibrotic responses to TGF-β. Thus, JunB represents an important target in diseases associated with EMT, including cancer and fibrosis.
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Gervasi
authors.forename: Anna
authors.initials: A
authors.lastname: Bianchi-Smiraglia
authors.forename: Michael
authors.initials: M
authors.lastname: Cummings
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zheng
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Bakin
mesh_terms: D000818:Animals; D002460:Cell Line; D021982:Cell-Matrix Junctions / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D016755:Proto-Oncogene Proteins c-jun; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta