國家衛生研究院 NHRI:Item 3990099045/3929
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3929


    Title: Pin1 promotes transforming growth factor-beta-induced migration and invasion
    Authors: Matsuura, I;Chiang, KN;Lai, CY;He, D;Wang, G;Ramkumar, R;Uchida, T;Ryo, A;Lu, K;Liu, F
    Contributors: Division of Molecular and Genomic Medicine
    Abstract: Transforming growth factor-beta (TGF-beta) regulates a wide variety of biological activities. It induces potent growth inhibitory responses in normal cells, but promotes migration and invasion of cancer cells. Smads mediate the TGF-beta responses. TGF-beta binding to the cell surface receptors leads to the phosphorylation of Smad2/3 in their carboxyl-terminus as well as in the proline-rich linker region. The serine/threonine phosphorylation sites in the linker region are followed by the proline residue. Pin1, a peptidyl-prolyl cis/trans isomerase, recognizes phosphorylated serine/threonine-proline (pS/T-P) motifs. Here we show that Smad2/3 interacts with Pin1 in a TGF-beta-dependent manner. We further show that the phosphorylated threonine 179-proline motif in the Smad3 linker region is the major binding site for Pin1. Although epidermal growth factor (EGF) also induces phosphorylation of threonine 179 and other residues in the Smad3 linker region same as TGF-beta, Pin1 is unable to bind to the EGF-stimulated Smad3. Further analysis suggests that phosphorylation of Smad3 in the carboxyl-terminus is necessary for the interaction with Pin1. Depletion of Pin1 by shRNA does not affect significantly on TGF-beta-induced growth-inhibitory responses and a number of TGF-beta/Smad target genes analyzed. In contrast, knockdown of Pin1 in human PC3 prostate cancer cells strongly inhibited TGF-beta-mediated migration and invasion. Accordingly, TGF-beta induction of N-cadherin, which plays an important role in migration and invasion, is markedly reduced when Pin1 is depleted in PC3 cells. Since Pin1 is overexpressed in many cancers, our findings highlight the importance of Pin1 in TGF-beta-induced migration and invasion of cancer cells.
    Date: 2010-01-15
    Relation: Journal of Biological Chemistry. 2009 Jan 15;285(3):1754-1764.
    Link to: http://dx.doi.org/10.1074/jbc.M109.063826
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000273429100021
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=76249090037
    Appears in Collections:[Isao Matsuura] Periodical Articles

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