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http://ir.nhri.org.tw/handle/3990099045/14206
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| Title: | Matriptase-2/NR4A3 axis switches TGF-beta action toward suppression of prostate cancer cell invasion, tumor growth, and metastasis |
| Other Titles: | Matriptase-2/NR4A3 axis switches TGF-β action toward suppression of prostate cancer cell invasion, tumor growth, and metastasis |
| Authors: | Lin, HY;Ko, CJ;Lo, TY;Wu, SR;Lan, SW;Huang, CA;Lin, YC;Lin, HH;Tu, HF;Lee, CF;Hsiao, PW;Huang, HP;Chen, MJ;Chang, KH;Lee, MS |
| Contributors: | Institute of Cellular and Systems Medicine |
| Abstract: | Dysregulation of pericellular proteolysis is strongly implicated in cancer metastasis through alteration of cell invasion and the microenvironment. Matriptase-2 (MT-2) is a membrane-anchored serine protease which can suppress prostate cancer (PCa) cell invasion. In this study, we showed that MT-2 was down-regulated in PCa and could suppress PCa cell motility, tumor growth, and metastasis. Using microarray and biochemical analysis, we found that MT-2 shifted TGF-beta action towards its tumor suppressor function by repressing epithelial-to-mesenchymal transition (EMT) and promoting Smad2 phosphorylation and nuclear accumulation to upregulate two TGF-beta 1 downstream effectors (p21 and PAI-1), culminating in hindrance of PCa cell motility and malignant growth. Mechanistically, MT-2 could dramatically up-regulate the expression of nuclear receptor NR4A3 via iron metabolism in PCa cells. MT-2-induced NR4A3 further coactivated Smad2 to activate p21 and PAI-1 expression. In addition, NR4A3 functioned as a suppressor of PCa and mediated MT-2 signaling to inhibit PCa tumorigenesis and metastasis. These results together indicate that NR4A3 sustains MT-2 signaling to suppress PCa cell invasion, tumor growth, and metastasis, and serves as a contextual factor for the TGF-beta/Smad2 signaling pathway in favor of tumor suppression via promoting p21 and PAI-1 expression. |
| Date: | 2022-05 |
| Relation: | Oncogene. 2022 May;41(20):2833-2845. |
| Link to: | http://dx.doi.org/10.1038/s41388-022-02303-z |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000783468200003 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85128236356 |
| Appears in Collections: | [張凱雄] 期刊論文
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| ISI000783468200003.pdf | | 7512Kb | Adobe PDF | 142 | View/Open |
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