Smad3 is key to TGF-β-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis
| Autor: | Christina H. Stuelten, Akira Ooshima, Kathleen C. Flanders, Fang Tian, Stacey DaCosta Byfield, Anita B. Roberts, Shizuya Saika |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pathology
medicine.medical_specialty Endocrinology Diabetes and Metabolism Immunology Cell medicine.disease_cause General Biochemistry Genetics and Molecular Biology law.invention Metastasis Mesoderm Transforming Growth Factor beta law Fibrosis Neoplasms medicine Animals Humans Immunology and Allergy Smad3 Protein Epithelial–mesenchymal transition Neoplasm Metastasis Cell Nucleus business.industry Cell Membrane Cell Differentiation Epithelial Cells medicine.disease medicine.anatomical_structure Cancer research Suppressor Signal transduction Carcinogenesis business Signal Transduction Transforming growth factor |
| Zdroj: | Cytokine & Growth Factor Reviews. 17:19-27 |
| ISSN: | 1359-6101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect