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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/8656
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Title: | A novel small-form NEDD4 regulates cell invasiveness and apoptosis to promote tumor metastasis |
Authors: | 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 |
Contributors: | Institute of Molecular and Genomic Medicine |
Abstract: | 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. |
Date: | 2015-03-20 |
Relation: | 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 |
Appears in Collections: | [黃秀芬] 期刊論文
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