國家衛生研究院 NHRI:Item 3990099045/11079
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    題名: PSPC1 mediates TGF-beta1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis
    其他題名: PSPC1 mediates TGF-β1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis
    作者: Yeh, HW;Hsu, EC;Lee, SS;Lang, YD;Lin, YC;Chang, CY;Lee, SY;Gu, DL;Shih, JH;Ho, CM;Chen, CF;Chen, CT;Tu, PH;Cheng, CF;Chen, RH;Yang, RB;Jou, YS
    貢獻者: Institute of Biotechnology and Pharmaceutical Research
    摘要: Activation of metastatic reprogramming is critical for tumour metastasis. However, more detailed knowledge of the underlying mechanism is needed to enable targeted intervention. Here, we show that paraspeckle component 1 (PSPC1), identified in an aberrant 13q12.11 locus, is upregulated and associated with poor survival in patients with cancer. PSPC1 promotes tumorigenesis, epithelial-to-mesenchymal transition (EMT), stemness and metastasis in multiple cell types and in spontaneous mouse cancer models. PSPC1 is the master activator for transcription factors of EMT and stemness and accompanies c-Myc activation to facilitate tumour growth. PSPC1 increases transforming growth factor-beta1 (TGF-beta1) secretion through an interaction with phosphorylated and nuclear Smad2/3 to potentiate TGF-beta1 autocrine signalling. Moreover, PSPC1 acts as a contextual determinant of the TGF-beta1 pro-metastatic switch to alter Smad2/3 binding preference from tumour-suppressor to pro-metastatic genes. Having validated the PSPC1-Smads-TGF-beta1 axis in various cancers, we conclude that PSPC1 is a master activator of pro-metastatic switches and a potential target for anti-metastasis drugs.
    日期: 2018-04
    關聯: Nature Cell Biology. 2018 Apr;20(4):479-491.
    Link to: http://dx.doi.org/10.1038/s41556-018-0062-y
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1465-7392&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000428781900017
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85044542236
    顯示於類別:[陳炯東] 期刊論文

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