國家衛生研究院 NHRI:Item 3990099045/8656
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    題名: A novel small-form NEDD4 regulates cell invasiveness and apoptosis to promote tumor metastasis
    作者: Liao, CJ;Chi, HC;Tsai, CY;Chen, C;Wu, SM;Tseng, YH;Lin, YH;Chung, IH;Chen, CY;Lin, SL;Huang, SF;Huang, YH;Lin, KH
    貢獻者: Institute of Molecular and Genomic Medicine
    摘要: Despite numerous investigations on metastasis, the determinants of metastatic processes remain unclear. We aimed to identify the metastasis-associated genes in hepatocellular carcinoma (HCC). Potent metastatic SK-hep-1 (SK) cells, designated 'SKM', were generated using Transwell assay followed by selection in a mouse model. Genes expressed differentially in SKM and SK cells were identified via microarray analyses. A small form of Neural precursor cell-expressed developmentally downregulated 4 (sNEDD4) was identified to be overexpressed in SKM cells, which was confirmed as a novel transcript using liquid chromatography-mass spectrometry. In clinical specimens, sNEDD4 was significantly overexpressed in tumors and serves as a poor prognostic factor for male patients with HCC (P = 0.035). Upon subcutaneous introduction of sNEDD4-overexpressing SK cells into flanks of nude mice, tumors grew faster than those of the control group. Furthermore, sNEDD4-mediated promotion of tumor metastasis was demonstrated in the orthotopic mouse model. Overexpression of sNEDD4 increased the invasive ability of SK cells through upregulation of matrix metalloproteinase 9 and inhibited serum deprivation-induced apoptosis via upregulation of myeloid cell leukemia 1. In conclusion, sNEDD4 is a novel metastasis-associated gene, which prevents apoptosis under nutrient restriction conditions. The present findings clearly support the prognostic potential of sNEDD4 for HCC.
    日期: 2015-03-20
    關聯: Oncotarget. 2015 Mar 20;6(11):9341-9354.
    Link to: http://dx.doi.org/10.18632/oncotarget.3322
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000358774600064
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84928735240
    顯示於類別:[黃秀芬] 期刊論文

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