國家衛生研究院 NHRI:Item 3990099045/2784
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    题名: CTGF enhances the motility of breast cancer cells via an integrin-alpha v beta 3-ERK1/2-dependent S100A4-upregulated pathway
    作者: Chen, PS;Wang, MY;Wu, SN;Su, JL;Hong, CC;Chuang, SE;Chen, MW;Hua, KT;Wu, YL;Cha, ST;Babu, MS;Chen, CN;Lee, PH;Chang, KJ;Kuo, ML
    贡献者: National Institute of Cancer Research
    摘要: Connective tissue growth factor ( CTGF) expression is elevated in advanced stages of breast cancer, but the regulatory role of CTGF in invasive breast cancer cell phenotypes is unclear. Presently, overexpression of CTGF in MCF-7 cells (MCF-7/CTGF cells) enhanced cellular migratory ability and spindle-like morphological alterations, as evidenced by actin polymerization and focal-adhesion-complex aggregation. Reducing the CTGF level in MDA-MB-231 (MDA231) cells by antisense CTGF cDNA (MDA231/AS cells) impaired cellular migration and promoted a change to an epithelial-like morphology. A neutralizing antibody against integrin alpha v beta 3 significantly attenuated CTGF-mediated ERK1/2 activation and cellular migration, indicating that the integrin-alpha v beta 3-ERK1/2 signaling pathway is crucial in mediating CTGF function. Moreover, the cDNA microarray analysis revealed CTGF-mediated regulation of the prometastatic gene S100A4. Transfection of MCF-7/CTGF cells with ASS100A4 reversed the CTGF-induced cellular migratory ability, whereas overexpression of S100A4 in MDA231/AS cells restored their high migratory ability. Genetic and pharmacological manipulations suggested that the CTGF-mediated S100A4 upregulation was dependent on ERK1/2 activation, with expression levels of CTGF and S100A4 being closely correlated with human breast tumors. We conclude that CTGF plays a crucial role in migratory/invasive processes in human breast cancer by a mechanism involving activation of the integrin-alpha v beta 3-ERK1/2-S100A4 pathway.
    关键词: Cell Biology
    日期: 2007-06-15
    關聯: Journal of Cell Science. 2007 Jun;120(12):2053-2065.
    Link to: http://dx.doi.org/10.1242/jcs.03460
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0021-9533&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000247024300011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34347363150
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