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10.1038/s41419-018-0657-z

http://scihub22266oqcxt.onion/10.1038/s41419-018-0657-z
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C5967338!5967338!29795373
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suck abstract from ncbi


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pmid29795373      Cell+Death+Dis 2018 ; 9 (6): ä
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  • Gamma synuclein is a novel Twist1 target that promotes TGF-?-induced cancer cell migration and invasion #MMPMID29795373
  • Shao T; Song P; Hua H; Zhang H; Sun X; Kong Q; Wang J; Luo T; Jiang Y
  • Cell Death Dis 2018[Jun]; 9 (6): ä PMID29795373show ga
  • Transforming growth factor ? (TGF-?) is critical for embryonic development, adult tissue homeostasis, and tumor progression. TGF-? suppresses tumors at early stage, but promotes metastasis at later stage through oncogenes such as Twist1. Gamma-synuclein (SNCG) is overexpressed in a variety of invasive and metastatic cancer. Here, we show that TGF-? induces SNCG expression by Smad-Twist1 axis, thus promoting TGF-?- and Twist1-induced cancer cell migration and invasion. We identify multiple Twist1-binding sites (E-boxes) in SNCG promoter. Chromatin immunoprecipitation and luciferase assays confirm the binding of Twist1 to the E-boxes of SNCG promoter sequence (?129/?1026?bp). Importantly, the Twist1-binding site close to the transcription initiation site is critical for the upregulation of SNCG expression by TGF-? and Twist1. Mutations of Twist1 motif on the SNCG promoter constructs markedly reduces the promoter activity. We further show that TGF-? induces Twist1 expression through Smad thereby enhancing the binding of Twist1 to SNCG promoter, upregulating SNCG promoter activity and increasing SNCG expression. SNCG knockdown abrogates TGF-?- or Twist1-induced cancer cell migration and invasion. Finally, SNCG knockdown inhibits the promotion of cancer metastasis by Twist1. Together, our data demonstrate that SNCG is a novel target of TGF-?-Smad-Twist1 axis and a mediator of Twist1-induced cancer metastasis.
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