title: Smad3 is key to TGF-beta-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis.
abstract: Smads2 and 3 transduce signals of TGF-beta from the cell surface to the nucleus. We used mice with a targeted deletion of Smad3 to study the specific contributions of this signaling pathway to pathogenic effects of TGF-beta. Focusing on models involving epithelial-to-mesenchymal transition (EMT), including injury to the lens and retina of the eye and to the kidney, we have found that loss of Smad3 blocks EMT and attenuates development of fibrotic sequelae. Smad3 also plays a critical role in both the tumor suppressor and pro-metastatic effects of TGF-beta in carcinogenesis. These observations suggest that development of small molecule inhibitors of Smad3 might have clinical application in treatment of fibrotic diseases as well as late stage cancers.
authors.affiliation: Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-5055, USA. Robertsa@dce41.nci.nih.gov
authors.forename: Anita B
authors.initials: AB
authors.lastname: Roberts
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.forename: Stacey DaCosta
authors.initials: SD
authors.lastname: Byfield
authors.forename: Christina
authors.initials: C
authors.lastname: Stuelten
authors.forename: Akira
authors.initials: A
authors.lastname: Ooshima
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Flanders
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
chemical_list: D051900:Smad3 Protein; D016212:Transforming Growth Factor beta