title: STAT3 selectively interacts with Smad3 to antagonize TGF-β signalling.
abstract: Smad and STAT proteins are critical signal transducers and transcription factors in controlling cell growth and tumorigenesis. Here we report that the STAT3 signaling pathway attenuates transforming growth factor-β (TGF-β)-induced responses through a direct Smad3-STAT3 interplay. Activated STAT3 blunts TGF-β-mediated signaling. Depletion of STAT3 promotes TGF-β-mediated transcriptional and physiological responses, including cell cycle arrest, apoptosis and epithelial-to-mesenchymal transition. STAT3 directly interacts with Smad3 in vivo and in vitro, resulting in attenuation of the Smad3-Smad4 complex formation and suppression of DNA-binding ability of Smad3. The N-terminal region of DNA-binding domain of STAT3 is responsible for the STAT3-Smad3 interaction and also indispensable for STAT3-mediated inhibition of TGF-β signaling. Thus, our finding illustrates a direct crosstalk between the STAT3 and Smad3 signaling pathways that may contribute to tumor development and inflammation.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China.|Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Sun
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery and the Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, School of Medicine Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: T
authors.initials: T
authors.lastname: Liang
authors.affiliation: Institute of Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhan
authors.affiliation: Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China.|Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA.|Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: X-H
authors.initials: XH
authors.lastname: Feng
mesh_terms: D002454:Cell Differentiation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000502:physiology*; D058504:Th17 Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D015850:Interleukin-6; C497790:SMAD3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor