Smad3 is key to TGF-β-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis

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• 作者：Anita B. Roberts ; Fang Tian ; Stacey DaCosta Byfield ; Christina Stuelten ; Akira Ooshima ; Shizuya Saika and Kathleen C. Flanders
• 关键词：Smad3 ; TGF-β ; EMT ; Fibrosis ; Metastasis
• 刊名：Cytokine and Growth Factor Reviews
• 出版年：2006
• 出版时间：February-April 2006
• 年：2006
• 卷：17
• 期：1-2
• 页码：19-27
• 全文大小：324 K

文摘

Smads2 and 3 transduce signals of TGF-β 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-β. 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-β 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.