title: SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis.
abstract: SND1 is an AEG-1/MTDH/LYRIC-binding protein that is upregulated in numerous human cancers, where it has been assigned multiple functional roles. In this study, we report its association with the TGFβ1 signaling pathway, which promotes epithelial-mesenchymal transition (EMT) in breast cancer. SND1 was upregulated in breast cancer tissues, in particular in primary invasive ductal carcinomas. Transcriptional activation of the SND1 gene was controlled by the TGFβ1/Smad pathway, specifically by activation of the Smad2/Smad3 complex. The SND1 promoter region contained several Smad-specific recognition domains (RD motifs), which were recognized and bound by the Smad complex that enhanced the transcriptional activation of SND1. We found that SND1 promoted expression of the E3 ubiquitin ligase Smurf1, leading to RhoA ubiquitination and degradation. RhoA degradation in breast cancer cells disrupted F-actin cytoskeletal organization, reduced cell adhesion, increased cell migration and invasion, and promoted metastasis. Overall, our results define a novel role for SND1 in regulating breast tumorigenesis and metastasis.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Cui
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Di
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Lingbiao
authors.initials: L
authors.lastname: Xin
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Minxin
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China. yangj@tijmu.edu.cn yaozhi@tijmu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, China. Tianjin Key Laboratory of Cellular and Molecular Immunology and Key Laboratory of the Educational Ministry of China, Tianjin Medical University, Tianjin, China. yangj@tijmu.edu.cn yaozhi@tijmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D004720:Endonucleases; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000502:physiology*; D059748:Proteolysis; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C066737:RHOA protein, human; C498342:SMURF1 protein, human; D044767:Ubiquitin-Protein Ligases; D004720:Endonucleases; C095221:SND1 protein, human; D020742:rhoA GTP-Binding Protein